Background Hospitalisation often leads to increased medication regimen complexity for older patients; increased complexity is associated with medication non-adherence. There has been little research into strategies for reducing the impact of hospitalisation on medication regimen complexity. Objective To investigate the impact of pharmacist medication review, together with an educational intervention targeting clinical pharmacists and junior medical officers, on the increase in medication regimen complexity that occurs during hospitalisation. Setting Two acute general medicine wards and two subacute aged care (geriatric assessment and rehabilitation) wards at a major metropolitan public hospital in Melbourne, Australia. Methods A before-after study involving patients aged 60 years and over was undertaken over two 5-week periods. During the pre-intervention period patients received usual care. During the intervention period, clinical pharmacists were encouraged to review patients’ medication regimen complexity prior to discharge, and make recommendations to hospital medical officers to simplify regimens. Prior to the intervention period, pharmacists attended an interactive case-based education session about medication regimen simplification, and completed an assessment task. A similar, but briefer, education session was delivered to junior medical officers. Main outcome measure The primary endpoint was change in medication regimen complexity index (MRCI) score (a validated measure of regimen complexity) between admission and discharge for regularly scheduled long-term medications, adjusted for age, length of hospital stay, number of medications and regimen complexity prior to admission. Results Three hundred ninety-one patients were included (mean age 80.6 years, mean 7.4 regularly scheduled long-term medications on admission). The mean increase in MRCI score between admission and discharge was significantly smaller in the 205 intervention patients than in the 186 usual care patients (2.5 vs. 4.0, p = 0.02; adjusted difference 1.6, 95 %CI 0.3, 2.9). The intervention had greatest impact in patients discharged from subacute wards (mean adjusted difference: 2.7), not using a dose administration aid after discharge (mean adjusted difference: 2.6), and not discharged to a residential care facility (mean adjusted difference: 1.9). Mean differences in MRCI scores were equivalent to ceasing one to two medications. Conclusion An educational intervention and clinical pharmacist medication review reduced the impact of hospitalisation on the complexity of older patients’ medication regimens.