Abstract Background Medication errors at transition of care can adversely affect patient safety. The objective of this study is to determine the effect of a transitional pharmaceutical care program on unplanned rehospitalisations. Methods An interrupted-time-series study was performed, including patients from the Internal Medicine department using at least one prescription drug. The program consisted of medication reconciliation, patient counselling at discharge, and communication to healthcare providers in primary care. The primary outcome was the proportion of patients with an unplanned rehospitalisation within six months post-discharge. Secondary outcomes were drug-related hospital visits, drug-related problems (DRPs), adherence, believes about medication, and patient satisfaction. Interrupted time series analysis was used for the primary outcome and descriptive statistics were performed for the secondary outcomes. Results In total 706 patients were included. At 6 months, the change in trend for unplanned rehospitalisations between usual care and the program group was non-significant (− 0.2, 95% CI -4.9;4.6). There was no significant difference for drug-related visits although visits due to medication reconciliation problems occurred less often (4 usual care versus 1 intervention). Interventions to prevent DRPs were present for all patients in the intervention group (mean: 10 interventions/patient). No effect was seen on adherence and beliefs about medication. Patients were significantly more satisfied with discharge counselling (68.9% usual care vs 87.1% program). Conclusions The transitional pharmaceutical care program showed no effect on unplanned rehospitalisations. This lack of effect is probably because the reason for rehospitalisations are multifactorial while the transitional care program focused on medication. There were less hospital visits due to medication reconciliation problems, but further large scale studies are needed due to the small number of drug-related visits. (Dutch trial register: NTR1519).