BackgroundThe steady rise in multimorbidity entails serious consequences for our populations, challenges healthcare systems, and calls for specific clinical approaches of proven effectiveness. The MULTIPAP Study comprises three sequential projects (MULTIPAP and MULTIPAP Plus RCTs, and the MULTIPAP Cohort). Results of MULTIPAP RCT are presented.AimTo evaluate the effectiveness of a complex, patient-centred intervention in young-old patients with multimorbidity and polypharmacy.MethodPragmatic cluster-randomised clinical trial in a primary healthcare setting. GPs were randomly allocated to either conventional care or the MULTIPAP intervention based on the Ariadne Principles with two components: GPs e-training (that is, eMULTIPAP addresses specific, key concepts on multimorbidity, polypharmacy and shared decision-making) and GP–patient-centred interview. Young-old patients aged 65–74 years with multimorbidity and polypharmacy were included. Main outcome: difference in the Medication Appropriateness Index (MAI) after 6-month follow-up between groups. Secondary outcomes: MAI, quality of life, patient perception, health services use, treatment adherence and cost-effectiveness after 12-month follow-up.Results117 GPs from 38 Spanish primary health care recruited 593 patients randomly assigned to the intervention/control groups. Difference in MAI scores between groups in the intention-to-treat analysis after 6 months’ follow-up: −2.42 (−4.27 to −0.59), P = 0.009 (adjusted difference in mean MAI score −1.81(−3.35 to −0.27), P = 0.021). Secondary outcomes: not significant, including quality of life (adjusted difference in mean EQ-5D-5L (VAS) 2.94 (−1.39 to 7.28), P = 0.183, EQ-5D-5L (index) −0.006(−0.034 to 0.022), P = 0.689).ConclusionThe intervention significantly improved medication appropriateness. The observed quality of life improvement was not significant. GPs e-training in multimorbidity has shown to be feasible and well accepted by the professionals. Future studies may test whether this format facilitates implementation.