Hospital readmissions are common among patients receiving multiple medications, with considerable costs to the patients and society.OBJECTIVE To determine whether a multifaceted pharmacist intervention based on medication review, patient interview, and follow-up can reduce the number of readmissions and emergency department (ED) visits. DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical multicenter study (Odense Pharmacist Trial Investigating Medication Interventions at Sector Transfer [OPTIMIST]) enrolled patients from September 1, 2013, through April 23, 2015, with a follow-up of 6 months completed on October 31, 2015. Consecutive medical patients in an acute admission ward who were 18 years or older and who used 5 or more medications were invited to participate. Of 1873 patients invited to participate, 1499 (80.0%) accepted. The medication review and patient interview were conducted in the hospital and followed up in collaboration with primary care. Analysis was based on intention to treat. INTERVENTIONSThe patients were randomized into 3 groups receiving usual care (no intervention), a basic intervention (medication review), and an extended intervention (medication review, 3 motivational interviews, and follow-up with the primary care physician, pharmacy, and nursing home). MAIN OUTCOMES AND MEASURESThe prespecified primary outcomes were readmission within 30 or 180 days and ED visits within 180 days. The primary composite end point was readmission or an ED visit within 180 days. Secondary outcomes were drug-related readmissions within 30 and 180 days after inclusion, and all-cause mortality and drug-related mortality.RESULTS A total of 1467 patients (679 men [46.3%] and 788 women [53.7%]; median age, 72 years; interquartile range, 63-80 years) were part of the primary analysis, including 498 randomized to usual care, 493 randomized to the basic intervention, and 476 randomized to the extended intervention. The extended intervention had a significant effect on the numbers of patients who were readmitted within 30 days (hazard ratio [HR], 0.62; 95% CI, 0.46-0.84) or within 180 days (HR, 0.75; 95% CI, 0.62-0.90) after inclusion and on the number of patients who experienced the primary composite end point (HR, 0.77; 95% CI, 0.64-0.93). The study showed a nonsignificant reduction in drug-related readmissions within 30 days (HR, 0.65; 95% CI, 0.39-1.09) and within 180 days (HR, 0.80; 95% CI, 0.59-1.08) after inclusion and in deaths (HR, 0.83; 95% CI,. The number needed to treat to achieve the primary composite outcome for the extended intervention (vs usual care) was 12.CONCLUSIONS AND RELEVANCE A multifaceted clinical pharmacist intervention may reduce the number of ED visits and hospital readmissions.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03079375