BACKGROUND: Multimorbidity is a major public health concern. Complex interventions, incorporating individualized care plans, may be appropriate for patients with multimorbidity given their individualized and variable needs. There is a dearth of evidence on the cost-effectiveness of complex multimorbidity interventions. OBJECTIVE: This study examines the cost-effectiveness of a 6-week occupational therapy-led self-management support programme (OPTIMAL) for adults with multimorbidity. METHODS: Economic evaluation, from a healthcare perspective, was conducted alongside a randomized controlled trial of 149 adults with multimorbidity. Intervention was the OPTIMAL programme with a comparison of usual primary care. Incremental costs, quality-adjusted life years (QALYs) gained, and expected cost-effectiveness were estimated at 6 months and uncertainty was explored using cost-effectiveness acceptability curves. RESULTS: The intervention was associated with a mean improvement in QALYs gained of 0.031 per patient (P-value: 0.063; 95% confidence intervals [CIs]: -0.002 to 0.063) and a mean reduction in total costs of €2,548 (P-value: 0.114; 95% CIs: -5,606 to 509) per patient. At cost-effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of the intervention being cost-effective was estimated to be 0.951 and 0.958, respectively. The results remained consistent across all subgroups examined. CONCLUSIONS: This study adds to the limited evidence base on the cost-effectiveness of complex interventions for multimorbidity, and highlights the potential for the OPTIMAL programme to be cost-effective. Further studies are warranted to explore the clinical and cost-effectiveness of complex interventions for the multimorbidity patient population, and for subgroups within it. TRIAL REGISTRATION: Trial number: ISRCTN67235963.