The protective role of serum total bilirubin, a widely recognized antioxidant, has been approved by numerous updating studies. However, regarding the effect of high serum total bilirubin level (STBL) in arteriosclerotic cardiovascular disease (ASCVD) are conflicting in different sources of data. We, therefore, performed this meta-analysis to evaluate the influence of STBL on risk of ASCVD.Four databases were used to identify the literature with a date of search of January, 2019. Finally, a total of 20 studies had been adopted. ASCVD was defined as acute coronary syndrome, stable angina, coronary revascularization, atherosclerotic stroke or transient ischemic attack, and peripheral arterial disease (PAD). All relevant data were collected from studies meeting the inclusion criteria.A total of 20 published studies (323,891 cases) met the inclusion criteria. The meta-analysis revealed that, in studies excluding heterogeneity, STBL was significantly positively related to in-hospital cardiovascular mortality (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.83-4.36, Z = 4.69, P < .001) and major adverse cardiac events (OR 1.88, 95% CI 1.414-2.491, Z = 4.36, P < .001), also negatively associated with prognosis of acute myocardial infarction, pooled hazard ratio (HR) = 0.804 (95% CI 0.700-0.923, Z = 3.08, P = .002). The correlation similarity was also reflected in terms of patients with stroke (HR 0.78, 95% CI 0.70-0.88, Z = 4.24, P = .003). Combined analysis revealed that lower STBL was significantly associated with PAD, pooled OR = 0.91 (95% CI 0.85-0.98, Z = 2.39, P = .017). In general analysis, a conclusion can be drawn, that higher STBL was significantly negative correlated with cardiovascular disease, pooled HR = 0.83 (95% CI 0.73-0.94, Z = 3.02, P = .003).Higher STBL significantly improved the prognosis of ASCVD; furthermore, STBL was an important factor in the long-term prognosis of vascular-related disease prevention and can be used as a predictor in vascular-related disease risk prediction.