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The resolution of potential drug-related problems is a priority of pharmaceutical care programmes.To assess the clinical impact on drug-related negative outcomes of a pharmaceutical care programme focusing on the resolution of potential drug-related problems, initiated in the emergency department for patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD).Controlled trials, in which older adults (≥65 years) receiving four or more medications admitted to the emergency department for ≥12 hours for worsening of HF and/or COPD were randomised (1:1) to either a pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department (intervention group (IG)) or standard care (control group). Comparisons between the groups were made for the proportion of patients with drug-related negative outcomes, number of drug-related negative outcomes per patient, mean stay, patients readmitted within 180 days and 180-day mortality.118 patients were included, 59 in each group. Fewer patients in the IG had drug-related negative outcomes (37 (62.7%) vs 47 (79.7%) in the control group (p=0.042)). Fewer drug-related negative outcomes per patient occurred in the IG (56 (0.95 per patient) vs 85 (1.44 per patient) in the control group (p=0.01)). The mean stay was similar between groups (194.7 hours in the IG vs 242.5 hours in the control group (p=0.186)). No difference in revisits within 180 days was found (32 (54.24%) in the IG vs 22 (37.3%) in the control group (p=0.065)). 180-Day mortality was detected in 11 (18.6%) patients in the IG compared with 13 (22%) in the control group (p=0.647).A pharmaceutical care programme focusing on resolving potential drug-related problems initiated at the emergency department has a favourable clinical impact, as it reduces the number and prevalence of drug-related negative outcomes. No difference was found in other outcome variables.Trial registration number NCT02368548.