BACKGROUND: Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Using Danish nationwide databases between 2010 and 2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well-balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazard ratio (HR) 0.97 (0.90–1.05) in patients with T2D versus 1.00 (0.95–1.05) for those without T2D, P for difference =0.99. Rates of new-onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75– 0.91), P<0.0001. CONCLUSIONS: In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long-term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new-onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.