Background: Restoring and maintaining sinus rhythm in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has been studied in clinical trials to reduce symptoms and improve quality of life. Limited data exist on the effectiveness of rate or rhythm control therapy in these patients. Methods: Consecutive patients with AF and ACS or referred for PCI were prospectively recruited in Fuwai Hospital during 2017-2020. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, non-central nervous system embolism and ischemia-driven revascularization. Kaplan-Meier curves and Cox regressions were performed to evaluate the association between rhythm/rate control and subsequent outcomes. For the primary endpoints, we used the Benjamini-Hochberg correction for multiple comparisons. Results: A total of 1499 patients with AF and ACS or undergoing PCI were included, with a median follow-up of 34.7 months. Compared to non-rate control, rate control strategy reduced the risk of subsequent MACCEs (adjusted HR, 0.320; 95 % CI 0.220-0.466; p <0.001; *p <0.002) and all-cause death (adjusted HR, 0.148; 95 % CI 0.093-0.236; p <0.001; *p <0.002). Similar trends were observed across all predefined subgroups (p <0.001). In the final multivariate model, rhythm control was not associated with a lower subsequent MACCEs but significantly improved all-cause mortality compared to non-rhythm control (adjusted HR, 0.546; 95 % CI 0.313-0.951; p =0.033; *p =0.044). Conclusions: In this real-world study, rate control strategy was associated with lower risk of MACCEs and all-cause death in AF and ACS or undergoing PCI. Besides, management with rhythm control strategy may improve all-cause mortality.