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Objectives To assess the effect of an intervention on drug-related problem ( DRP; adverse drug reactions, adherence problems, underuse)-related readmission rates in older adults. Design Ancillary study from a 6-month, prospective, randomized, parallel-group, open-label trial. Setting Six acute geriatric units in Paris and suburbs. Participants Six hundred sixty-five consecutively admitted individuals were included: 317 in the intervention group ( IG) and 348 in the control group ( CG) (aged 86.1 ± 6.2, 66% female). Intervention Discharge-planning intervention combining chronic drug review, education, and enhanced transition-of-care communication. Measurements Chronic drugs at discharge of the two groups were compared. An expert committee blinded to group assignment adjudicated whether 6-month readmission to the study hospitals was related to drugs. Results Six hundred thirty-nine individuals were discharged and followed up (300 IG, 339 CG). The intervention had no significant effect on drug regimen at discharge, characterized by prescriptions that are mostly appropriate but increase iatrogenic risk. Three hundred eleven readmissions occurred during follow-up (180 CG, 131 IG), of which 185 (59.5%) were adjudicated (102 CG, 83 IG). For 16, DRP imputability was doubtful. Of the remaining 169, DRPs were the most frequent cause for readmission, with 38 (40.4%) readmissions in the CG and 26 (34.7%) in the IG (relative risk reduction = 14.3%, 95% confidence interval = 14.0-14.5%, P = .54). The intervention was associated with 39.7% fewer readmissions related to adverse drug reactions ( P = .12) despite the study's lack of power. Conclusion Drug-related problem prevention in older people discharged from the hospital should be a priority, with a focus on improving the monitoring of drugs with high iatrogenic risk. [ABSTRACT FROM AUTHOR]