It has been reported that selective serotonin reuptake inhibitors (SSRIs) might induce major adverse cardiovascular events (MACE), but the association between the use of SSRIs and MACE has not been elucidated as yet. Therefore, the aim of this study was to evaluate the association between the use of SSRIs and MACE in depressed patients with previous cardiovascular events. Two researchers independently selected randomized-controlled studies (RCTs) according to the predefined inclusion criteria and evaluated the quality of articles. A quantitative analysis was carried out to estimate pooled risk ratios (RRs) for the association between the use of SSRIs and MACE. Ten RCTs were selected in the final analysis. The use of SSRIs in depressed patients with previous cardiovascular events significantly decreased the risk of MACE [RR: 0.74; 95% confidence interval (CI): 0.55–0.99]. The risk of myocardial infarction was also reduced significantly (RR: 0.59, 95% CI: 0.37-0.93), associations with stroke and all-cause-death (cardiac or other causes): risk of stroke (RR: 0.88, 95% CI: 0.35-2.25) or all-cause death (RR: 0.83; 95% CI: 0.66-1.05). This meta-analysis suggests that the use of SSRIs decreased the risk of MACE by significantly reducing the risk of myocardial infraction in patients with depression and previous cardiovascular events.