Characterizing the potential health effects of exposure to risk factors such as red meat consumption is essential to inform health policy and practice. Previous meta-analyses evaluating the effects of red meat intake have generated mixed findings and do not formally assess evidence strength. Here, we conducted a systematic review and implemented a meta-regression—relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity—to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. We found weak evidence of association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, we found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke. We also found that while risk for the six outcomes in our analysis combined was minimized at 0 g unprocessed red meat intake per day, the 95% uncertainty interval that incorporated between-study heterogeneity was very wide: from 0–200 g d−1. While there is some evidence that eating unprocessed red meat is associated with increased risk of disease incidence and mortality, it is weak and insufficient to make stronger or more conclusive recommendations. More rigorous, well-powered research is needed to better understand and quantify the relationship between consumption of unprocessed red meat and chronic disease. Using the burden of proof analytical tool, a meta-analysis found weak or no evidence of associations between unprocessed red meat consumption and increased risk of six cardiometabolic disease and cancer outcomes. The Global Burden of Diseases, Injuries and Risk Factors study (GBD) 2019 estimated that 896,000 (95% uncertainty interval (UI) 536,000–1,250,000) deaths and 23.9 million Based on such evidence and in light of limited existing information on the shape of the risk curves for red meat and different health outcomes, it is plausible that the health effects of red meat consumption may not be well characterized by a log-linear function and should be investigated more closely. Another notable issue is that meta-analyses attempting to synthesize findings from cohort studies typically do not account for between-study heterogeneity, which can be a prominent source of bias in epidemiological meta-analyses 19 . In this paper we examined the relationship between unprocessed red meat and six health outcomes: breast cancer, colorectal cancer, type 2 diabetes, ischemic heart disease (IHD), ischemic stroke and hemorrhagic stroke. These outcomes were selected using the WCRF criteria for convincing or probable evidence 7 . To rigorously quantify the dose–response relationship between unprocessed red meat consumption and the selected health outcomes—in addition to the strength of the evidence underlying the results—we systematically evaluated all available prospective epidemiological evidence on the association between unprocessed red meat consumption and each selected health outcome following the burden of proof risk function (BPRF) methodology developed by Zheng et al. 20 . Policy implications The available evidence suggests that elevated unprocessed red meat has a weak association with the risk of colorectal cancer, breast cancer, IHD and type 2 diabetes. It may have an effect on ischemic stroke or hemorrhagic stroke, but there is currently insufficient evidence to draw this conclusion. The available evidence suggests that eating no unprocessed red meat may minimize the risk of disease incidence and mortality compared to consuming any, but there is insufficient evidence to make stronger or more conclusive recommendations. The level of red meat intake to optimize physical health is the subject of much interest and there is a wide range of recommendations in the literature 6 – 10 . By aggregating the outcome-specific risk curves computed in the present analysis, we generated a RR curve for the six outcomes combined that minimized risk at 0 g d −1 (95% UI 0–200) of unprocessed red meat consumption. This mean minimum risk is lower than the intake level recommended by the EAT-Lancet Commission (14 g d −1 ) 8 . For instance, a risk factor with high prevalence of exposure and a two-star relationship with a common and serious health outcome might warrant more policy focus than a risk factor with lower prevalence of exposure and a three-star or four-star relationship with a rare or less severe health outcome. The star rating for a risk–outcome pair is just one component to consider when making policy recommendations, but its compatibility with GBD estimates adds value to our approach. Our analysis found a high degree of between-study heterogeneity and uncertainty in the existing body of evidence on the health effects of red meat intake. When all forms of uncertainty including between-study heterogeneity were incorporated, we found weak evidence of associations between unprocessed red meat consumption and colorectal cancer, breast cancer, IHD and type 2 diabetes. The available data were consistent with no association between unprocessed red meat consumption and ischemic stroke and hemorrhagic stroke, which received one-star ratings. While there is some evidence that eating red meat increases risk of chronic disease, there is insufficient evidence to make stronger or more conclusive recommendations. More rigorous, well-powered research is needed to better understand and quantify the relationship between red meat consumption and chronic disease. Finally, to aid interpretability of our findings for policy makers and research funders, we converted the ROSs to star-rating categories from one to five, with a higher rating indicating that the evidence for and magnitude of a relationship between risk and outcome is stronger. The conservative interpretation suggests that, for one-star pairs, there may be no true association between risk exposure and health outcome.