Background <p>Rosuvastatin and atorvastatin are the two primary high-intensity statins used for cardiovascular risk reduction. However, concerns have been raised regarding the renal safety profile of rosuvastatin. This study compared risks of hematuria, proteinuria, and cardiovascular events between rosuvastatin- and atorvastatin-treated patients.</p> Methods <p>This is a retrospective cohort study of atorvastatin and rosuvastatin users from 1 January 2018 to 31 December 2021. Inverse probability of treatment weighting was used to mitigate confounding. Poisson regression models were used to estimate adjusted relative risks.</p> Results <p>Of 136,680 patients (median age 61 years, 42.6% female), 46,292 were treated with atorvastatin and 90,388 rosuvastatin. During follow-up, there were 619 cases of proteinuria, 1843 cases of hematuria, and 19 cases of end-stage renal disease. Compared with atorvastatin, rosuvastatin was associated with a nonsignificant increase in the risk of hematuria (adjusted risk ratio [aRR] 1.1, 95% confidence interval [CI] 0.98–1.24) and proteinuria (aRR 1.02, 95% CI 0.83–1.25). Risk of cardiovascular events was significantly lower with rosuvastatin (aRR 0.77, 95% CI 0.70–0.83). Rosuvastatin was associated with a lower risk of myocardial infarction (aRR 0.75, 95% CI 0.63–0.91) and stroke (aRR 0.76, 95% CI 0.62–0.94) but not heart failure (aRR 0.82, 95% CI 0.63–1.06). Significant cardiovascular risk reduction was observed with rosuvastatin in the first 6 months.</p> Conclusions and Relevance <p>Compared with atorvastatin, rosuvastatin was associated with a significantly lower risk of cardiovascular events and a nonsignificant increase in hematuria and proteinuria. Overall, the cardiovascular benefits of rosuvastatin appear to outweigh the minor renal risks.</p>