Medical students may not be adequately trained to prescribe appropriately to older adults with polypharmacy. This study addressed how to teach students to minimize inappropriate polypharmacy. Final-year medical students (N = 106) from two Dutch schools of medicine participated in this randomized controlled trial with a pre/posttest design. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) was used as the intervention. This medication review tool consists of five steps and is part of the Dutch multidisciplinary guideline on polypharmacy. Step two is a structured pharmaceutical analysis of drug use, assessed using six questions regarding undertreatment, ineffective treatment, overtreatment, potential adverse effects, contraindications or interactions, and dose adjustments. It is used in combination with the Screening Tool to Alert doctors to Right Treatment and the Screening Tool of Older Person's Prescriptions checklists. Students were asked to optimize the medication lists of real people, making use, or not, of the STRIP. The number of correct or potentially harmful decisions that the students made when revising the lists was determined by comparison with expert consensus. Students who used the STRIP had better scores than control students; they made more correct decisions (9.3 vs 7.0, 34%; P < .001, correlation coefficient (r) = 0.365) and fewer potentially harmful decisions (3.9 vs 5.6, −30%; P < .001, r = 0.386). E-learning did not have a different effect from that of non-E-learning methods. Students were satisfied with the method. The STRIP method is effective in helping final-year medical students improve their prescribing skills.