AIMS: The aim of this study was to assess whether a pharmacist intervention associating medication reconciliation at discharge with a link to the community pharmacist reduces drug-related problems (DRP) in adult patients during the 7 days after hospital discharge in 22 university or general hospitals in France. METHODS: We conducted a cluster randomised cross-over superiority trial with hospital units as the cluster unit. The primary outcome was a composite of any kind of DRP (prescription/dispensation, patient error or gap due to no medication available) during the 7 days after discharge, assessed by phone with the patient and community pharmacist. Among secondary outcomes, we studied self-reported unplanned hospitalisations at day 35 after discharge and severe iatrogenic problems. RESULTS: A total of 1092 patients were enrolled in 48 units (538 in the experimental periods and 554 in the control periods). Three patients refused to have their data analysed and were excluded from the analyses. As compared with usual care, the pharmacist intervention led to a lower proportion of patients with at least one DRP (44.0% vs 50.6%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.61-0.98) and severe iatrogenic problems (5.2% vs 8.7%; OR 0.57, 95% CI 0.35-0.93) but no significant difference in unplanned hospitalisations at day 35 (5.8% vs 4.5%; OR 1.46, 95% CI 0.91-2.35). CONCLUSION: Medication reconciliation associated with communication between the hospital and community pharmacist may decrease patient exposure to DRP and severe iatrogenic problems but not unplanned hospitalisation. However, this intervention could be recommended in health policies to improve drug management.