Background A clinical medication review, including patient involvement, is expected to improve pharmaceutical care. Objective To determine whether a clinical medication review followed by a pharmaceutical care plan decreases the number of potential drug-related problems (DRPs) and pharmaceutical care issues (PCIs) and leads to a positive effect on relevant clinical and laboratory parameters for elderly cardiovascular patients with multiple drug use. Setting Randomized controlled trial in eight primary care settings in the Netherlands. Method Elderly polypharmacy patients with a cardiovascular disorder were randomized into two groups. Intervention patients received a clinical medication review, followed by a pharmaceutical care plan developed in cooperation between these patients' pharmacists and general practitioners (GPs), and agreed to by the patients. Control patients received care as usual. Patient data were collected at the start of the study (t = 0) and after 1-year follow-up (t = 1). Main outcome measure Decrease in potential DRPs and pharmaceutical PCIs, improvement of clinical and laboratory parameters. Results 512 patients were included. An average of 2.2 potential DRPs and pharmaceutical PCIs were defined per patient in the intervention group. After 1-year follow-up, 47.2 % of potential DRPs and PCIs were resolved. In total, 156 care interventions were proposed (0.9/patient), 108 of which were implemented after 1 year (69.2 %). For control-group patients, a total of 47 proposed care interventions were documented for 255 patients (0.2/patient); after 1 year, 43 had been implemented (91.5 %). The study intervention (p <0.001) and the number of medicines used (p = 0.030) had a significant effect on the number of interventions proposed. Small biochemical changes in cardiovascular risk factors did occur, but the differences were small and not considered clinically relevant. Conclusion The integrated use of a clinical medication review with a pharmaceutical care plan in a primary care setting supports ...