Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66–0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66–0.76) and non-CVD studies (0.70, 0.67–0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61–0.73) and the lowest in studies from North America (0.78, 0.73–0.83) and Australia (0.78, 0.62–0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD.