The authors tested the effectiveness and estimated the cost of several interventions aimed at reducing drug interactions in primary care by designing a 15-month cluster-controlled trial. The trial involved 265 family physicians and their patients who were randomized into 4 groups: control, report (received feedback reports), session (group sessions), and face-to-face (personal interviews). The outcome was the mean of relevant interactions detected on electronic medical records. Cost-effectiveness was defined as the incremental cost to reduce drug interactions by 1%. The authors detected a baseline mean of 6.7 interactions per 100 patients, which was reduced to 5.3 interactions after follow-up. No improvement was seen in the report group when compared with the control group, whereas progressive improvement in the other groups was noted (P < .001). Incremental cost was higher in the face-to-face group (69.4€ vs 50.7€); cost-effectiveness results were slightly better in the session group (4.2€ vs 4.5€).