Syringe aspiration when vaccinating intramuscularly was not recommended before the pandemic due to the lack of conclusive evidence that it provides any benefit. However, in vivo evidence suggests that intravenous injection of mRNA vaccine can potentially lead to myocarditis, while introducing adenoviral vector to bloodstream can possibly result in thrombocytopenia and coagulopathy. These rare reactions were recorded in humans following the administration of the COVID-19 vaccines. Although the syringe aspiration may increase the level of pain at the injection site, it represents a simple technique to decrease the risk of vaccine introduction into the vascular system and potentially decrease the risk of severe reactions to mRNA and adenoviral vaccines. We are of the opinion that this cannot be disregarded if one considers that the COVID-19 vaccines will continue to be administrated globally in the form of initial and booster doses. Therefore, the aspiration when giving mRNA and adenoviral vaccines appears to be fully in line with the precautionary principle. Although the syringe aspiration may increase the level of pain at the injection site, it represents a simple technique to decrease the risk of vaccine introduction into the vascular system and potentially decrease the risk of severe reactions to mRNA and adenoviral vaccines. We are of the opinion that this cannot be disregarded if one considers that the COVID-19 vaccines will continue to be administrated globally in the form of initial and booster doses. Therefore, the aspiration when giving mRNA and adenoviral vaccines appears to be fully in line with the precautionary principle. Notably, some of these events were documented in animals after an intravenous vaccine administration, i.e., heart inflammation in case of mRNA vaccine [ 16 ] and acute thrombocytopenia and coagulopathy in the case of the adenoviral vector vaccine [ 13 ]. These observations fuel the discussion of whether the administration of the COVID-19 vaccines should be preceded with the syringe aspiration for 5–10 s after the needle is introduced intramuscularly [ 17 , 18 ]. This technique was specifically developed in the past to ensure the medication is not inadvertently delivered into a blood vessel. The aspiration is sometimes performed at various COVID-19 vaccination points depending on the approach of local consensuses or healthcare personnel habits. This paper briefly presents the pros and cons of these practices, explicitly addressing mRNA and adenoviral vaccines, to help in further considerations regarding the aspiration during the global COVID-19 vaccination campaigns. Arguments favoring aspiration during COVID-19 vaccination Aspiration is a technique practiced to avoid accidental vaccine injection into a vessel during intramuscular administration. The appearance of blood in the syringe indicates that this is a case and shall result in another vaccination attempt. In this situation, the needle should be withdrawn, the syringe discarded, and another injection (prepared using new vaccine dose and equipment) should be given in a different location [ 17 , 23 ]. The deltoid muscle is the preferred injection site for SARS-CoV-2 vaccines. Although the usual spot, 5–7 cm As shown in vivo in mice, intravenous injection of the BNT162b2 vaccine (BioNTech/Pfizer, Germany/USA) resulted in histopathological changes characteristic for myopericarditis. Two days after treatment, the animals revealed calcific deposits on the visceral pericardium, interstitial edema, pericardial and myocardial infiltration of white blood cells, and transiently upregulated inflammatory cytokines and chemokines cardiomyocytes degeneration, apoptosis, and necrosis. The serum troponin levels were also markedly elevated. All in all, rare translocation of adenoviral vector outside the injection site may potentially result in its interaction with platelets and increase the risk of thrombosis. However, one should note that each intramuscularly injected dose of the COVID-19 adenoviral vaccines contains approximately 5 × 10 10 viral particles [ 41 , 42 ]. Thus, improper vaccine administration can potentially lead to their rapid appearance and high presence in the blood. Therefore, it is essential for the vaccinators to thoroughly understand the anatomy and landmarks of the injection site to decrease the potential risk associated with the elimination of the aspiration technique [ 19 ]. Notably, the deltoid muscle, the recommended site for COVID-19 vaccines’ administration, does not have the proximity of major blood vessels [ 20 ] except the posterior circumflex humeral artery. However, it must be kept in mind that several branches of the posterior circumflex humeral artery supply the middle and posterior portions of the deltoid. It can be argued, though, that lack of aspiration and subsequent accidental introduction of the vaccine into the bloodstream cannot be responsible for all acute cases of myocarditis/pericarditis after mRNA vaccines or thrombotic thrombocytopenia after vaccination with adenoviral vaccines. This is due to demographical differences in incidences of these events, e.g., heart inflammation significantly more frequently reported after vaccination in younger, male adults [ 6 ]. Young males have substantially higher muscle mass, greater muscle thickness with more blood vessels. The injection technique and sometimes needle size must be individually adjusted. Although COVID-19 vaccines are intended for intramuscular injection, the deltoid muscle, a preferred site, has enough vascularity to accidentally and rarely lead to the vaccine’s introduction into the bloodstream and its translocation to distant tissues. Although the aspiration may increase the level of pain at the injection site, it represents a simple technique to decrease the risk of vaccine introduction into the vascular system. It can potentially reduce the risk of acute severe reactions to mRNA and adenoviral vaccines.