To evaluate the effectiveness of an optimized Participation for Medication Safety (PFMS) program in promoting older adults’ participation in medication safety during the hospital-to-home transition. A randomized controlled trial was conducted among older inpatients with chronic diseases discharged from two tertiary hospitals in Fuzhou in August 2024. Participants were randomly allocated to an intervention group ( n = 56) or control group ( n = 55). The PFMS Program included: two one-on-one, face-to-face sessions on medication discrepancies review and teach-back medication education before discharge (30–60 min each); and six weekly remote motivational interviewing sessions via WeChat video calls during the 6-week post-discharge period (10–20 min each). The control group received routine care. Analyses followed the intention-to-treat principle using Generalized Linear Mixed Models (GLMM). A total of 111 valid cases were included, with 92 completing follow-up. The GLMM analysis showed that, at 3 months after discharge, the intervention group had significantly higher scores for patient participation in medication safety (β = 15.461, 95% CI: 10.631, 20.292, p < 0.001) and health literacy (β = 7.053, 95% CI: 2.814, 11.291, p < 0.05) than the control group. The odds of medication discrepancies were also significantly lower in the intervention group (OR = 0.128, 95% CI: 0.045, 0.362, p < 0.001). The omnibus group effects were statistically significant for self-efficacy (F = 6.550, p < 0.05) and healthcare provider support (F = 6.842, p < 0.05), whereas the between-group differences at 3 months after discharge were not statistically significant (self-efficacy: β = 0.129, 95% CI: −0.099, 0.358, p > 0.05; healthcare provider support: β = 0.892, 95% CI: −1.725, 3.509, p > 0.05). Between-group differences in these two outcomes were observed only at 6 weeks after discharge (both p < 0.05). The PFMS program improved participation in medication safety and health literacy and reduced medication discrepancies among older adults with chronic diseases during the hospital-to-home transition. Short-term between-group differences in self-efficacy and healthcare provider support were observed at the end of the intervention but were not maintained at 3 months after discharge. The trial was registered in the Chinese Clinical Trial Registry on April 18, 2024 (ChiCTR2400083215).
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