Self-medication (SM) forms an important part of public health strategy. Nonetheless, little research has been performed to understand the current state of self-medication in the European Union (EU). Utilizing data from the third wave of the European Health Interview Surveys, this study finds an estimated SM prevalence of 34.3% in the EU (95%CI = 34.1-34.5%; n = 255,758). SM prevalence, as well as SM prevalence inequality between men and women, varies substantially between EU member countries. Via multivariable analysis, we also identify a number of variables associated with SM, most notably the substantial impact of health systems on SM behavior (Adjusted Odds Ratio [AOR] = 4.00; 95% Confidence Interval [95%CI] = 3.81–4.21). Several demographics are also associated with greater SM prevalence, including those aged 25–44 (versus ages 75+: AOR = 1.21; 95%CI = 1.12–1.31), women (AOR = 1.74; 95%CI = 1.68–1.81), immigrants born in other EU states (AOR = 1.16; 95%CI = 1.04–1.30), those with higher education (AOR = 1.83; 95%CI = 1.60–2.09), and urban dwellers (AOR = 1.14; 95%CI = 1.04–1.30). Additionally, long-standing health problems (AOR = 1.39; 95%CI = 1.33–1.45), visits to doctors (both general practitioners and specialists) (AOR = 1.21, 95%CIs = 1.15–1.26, 1.17–1.26), and unmet needs for health care due to waiting lists (AOR = 1.38; 95%CI = 1.23–1.55) or inability to afford medical examinations/treatment (AOR = 1.27; 95%CI = 1.12–1.42) serve as conditioners for SM. We also find that smoking (AOR = 1.05; 95%CI = 1.01–1.10), vaping (AOR = 1.19; 95%CI = 1.06–1.32), drinking alcohol (AOR = 1.23; 95%CI = 1.19–1.28), and higher levels of physical activity (AOR = 1.27; 95%CI = 1.22–1.32) are factors associated with SM. Analysis of these variables reveals that though women self-medicate more than men, the patterns that govern their consumption are similar.