Cocaine was a known cardiovascular toxin, although its effect on clinical outcomes in heart failure (HF) remained uncertain. Although nonselective β-blocker medication appeared to be well tolerated in cocaine users with heart failure and decreased ejection fraction (HFrEF), selective β-blockers have not been examined. For a study, researchers sought to determine if cocaine use was related to worse clinical outcomes in patients with heart failure and to test the safety of β-blocker prescription upon discharge in cocaine users with HFrEF. It was a retrospective cohort analysis of individuals hospitalized with incident HF at a safety-net institution. The primary outcomes were all-cause mortality and readmissions, including heart failure (HF). Cocaine users were compared to non-users of the same age, gender, and index admission year. The outcomes of cocaine users with HFrEF were compared based on the β-blocker prescription at discharge. From 2001 to 2019, 738 cocaine users and 738 matched nonusers were found and compared. Cocaine use was linked with higher 1-year mortality (adjusted hazard ratio [HR] 1.21; 95% CI 1.00 to 1.48) and 90-day readmission (all-cause: adjusted HR 1.49; 95% CI 1.20 to 1.85; HF: adjusted HR 1.49; 95% CI 1.10 to 2.01). In cocaine users discharged with a prescription for metoprolol, carvedilol, or no β-blocker, the 1-year mortality and 30-day readmission rates were comparable. Cocaine usage was related to higher all-cause mortality, readmission for heart failure, and all-cause readmission. Both nonselective and selective β-blockers might be safe for cocaine-using patients with HFrEF.