Background: To comprehensively review the literature and synthesize evidence concerning the relationship between preadmission calcium channel blocker (CCB) use and mortality in patients with sepsis.Methods: The MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched from their inception to April 9, 2020. Cohort studies that related to prior CCB use in patients with sepsis were analysed. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. Two primary outcomes related to mortality, namely, 30-day mortality and 90-day mortality, were analysed; heterogeneity between studies was assessed using I2 and was considered moderate if I2 was equivalent to 50–75% and high if I2 ≥ 75%. Fixed and random-effects models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). The quality of outcomes was evaluated with the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were performed to examine the robustness of the results.Results: 552 potentially relevant studies were identified, and the full texts of 25 articles were reviewed. Ultimately, five cohort studies involving 280,982 patients were confirmed to have a low risk of bias and were included. Preadmission CCB use was associated with a significantly lower 30-day mortality in septic shock (OR, 0.61 [0.38-0.97]; P = 0.035; I2 = 62.4%), not in sepsis (OR, 0.83 [0.66-1.04]; P = 0.103; I2 = 95.4%). Moreover, prior CCB use could significantly reduce 30-day mortality in sepsis (OR, 0.90 [0.85-0.95]; P < 0.001; I2 = 31.9%). Conclusions: This meta-analysis suggests that preadmission CCB use is significantly associated with improving long-term prognosis of sepsis, and also short-term survival of septic shock patients. This finding may provide an attractive direction for sepsis management.