Abstract Background The benefit of β-blockers post-myocardial infarction (MI) was established in the late 1970s. Major advances in the treatment of MI have since occurred. However, patients with chronic heart failure (CHF) were excluded from those trials. The purpose of this study was to assess the effect of β-blockers in post-MI patients with CHF receiving contemporary management. Methods This was a prespecified subgroup analysis of a double-blind, randomized trial: the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF). Patients with CHF in New York Heart Association class II to IV with an ejection fraction (EF) ≤0.40 and a history of being hospitalized for an acute MI (n = 1926) were randomized to metoprolol succinate controlled release/extended release (CR/XL) versus placebo. Mean EF was 0.28, and the mean follow-up was 1 year. Results Metoprolol CR/XL reduced total mortality by 40% (95% CI 0.20–0.55, P = .0004), and sudden death by 50% (95% CI 0.26–0.66, P = .0004). The combined end point of all-cause mortality/hospitalization for worsening CHF was reduced by 31% (95% CI 0.16–0.44, P < .0001), and cardiac death/nonfatal acute MI by 45% (95% CI 0.26–0.58, P < .0001). A post-hoc analysis showed that the outcome in patients with earlier revascularization (44%) and outcome in those with more severe CHF (20%) was similar to the entire post-MI population. Conclusions In post-MI patients with symptomatic CHF, β-blockade continues to exert a profound reduction in mortality and morbidity in the presence of contemporary management that includes early and late revascularization, angiotensin-converting enzyme inhibitors, aspirin, and statins.