Background: Carvedilol, a non-selective β- and α1-blocker, is available in immediate-release (IR) and slow-release (SR) formulations. While carvedilol IR requires twice-daily dosing, SR was developed to improve adherence by allowing once-daily administration. This study aimed to compare long-term clinical outcomes between SR and IR carvedilol. Methods: A total of 38,563 patients taking either SR (n = 6223) or IR carvedilol (n = 32,340) were retrospectively analyzed using national claims data. Baseline characteristics, medication adherence, and cardiovascular outcomes were evaluated over a median follow-up period of 730 days. Multivariable Cox regression analyses were performed to adjust for potential confounders. Results: Despite a higher burden of comorbidities in the SR group, patients taking SR carvedilol had significantly lower risks of major adverse cardiovascular events (MACE), non-fatal myocardial infarction, and heart failure hospitalization compared to those on IR carvedilol. The adjusted hazard ratio for MACE with SR compared to IR was 0.61 (95% CI, 0.556-0.670; p < 0.001). No significant difference in non-fatal stroke was observed between the groups. Conclusions: In this claims-based observational cohort, SR carvedilol was associated with more favorable long-term cardiovascular outcomes than IR carvedilol. However, this association does not establish causal superiority, and prospective randomized studies are needed to confirm these findings.