BACKGROUND AND OBJECTIVES: Multidisciplinary transitional care interventions (MTCIs) ensure care coordination and continuity after hospital discharge while addressing (older) patients' complex care needs related to their physical, nutritional, cognitive, and/or psychological status. This study aimed to identify, critically appraise, and synthesize the current body of evidence investigating the effectiveness of such interventions. RESEARCH DESIGN AND METHODS: Medline, Embase, CINAHL, and CENTRAL were searched for randomized controlled trials assessing MTCIs' impact on readmissions, mortality, and health-related outcomes from inception to July 2024. Risk of bias was evaluated with the Risk of Bias-2 tool. Subgroup analyses assessed whether different intervention types affected outcomes differently. The certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach and the credibility of subgroup analyses with the Instrument to evaluate the Credibility of Effect Modification Analyses. RESULTS: Forty-nine trials involving 25,566 patients were included. There was low certainty that MTCIs reduced readmissions (relative risk [RR] = 0.88
95% confidence intervals [95% CI] = 0.80 to 0.96) and high certainty for reduced mortality (RR = 0.92
95% CI = 0.84 to 1.01). There was low to moderate certainty that MTCIs improved physical quality of life (standardized mean difference [SMD] = 0.54
95% CI = -0.06 to 1.15), mental quality of life (SMD = 0.44
95% CI = -0.08 to 0.96), patient satisfaction (SMD = 0.49
95% CI = -0.14 to 1.12), and physical performance (SMD = 0.49
95% CI = -0.11 to 1.10). Subgroup analysis revealed a larger and statistically significant effect on physical performance in more complex interventions (SMD = 0.83
95% CI = 0.02 to 1.65). DISCUSSION AND IMPLICATIONS: These findings suggest that MTCIs can reduce readmissions and mortality while improving quality of life and physical performance. Further investigations should focus on tailoring MTCIs to specific contexts to maximize their impact.