Older people with multi-morbidity are increasingly challenging for today's healthcare, and novel, cost-effective healthcare solutions are needed. The aim of this study was to assess the cost-effectiveness of comprehensive geriatric assessment (CGA) at an ambulatory geriatric unit for people ≥75 years with multi-morbidity. The primary outcome was the incremental cost-effectiveness ratio (ICER) comparing costs and quality-adjusted life years (QALYs) of a CGA strategy with usual care in a Swedish setting. Outcomes were estimated over a lifelong time horizon using decision-analytic modelling based on data from the randomized AGe-FIT trial. The analysis employed a public health care sector perspective. Costs and QALYs were discounted by 3% per annum and are reported in 2016 euros. Compared with usual care CGA was associated with a per patient mean incremental cost of approximately 25,000 EUR and a gain of 0.54 QALYs resulting in an ICER of 46,000 EUR. The incremental costs were primarily caused by intervention costs and costs associated with increased survival, whereas the gain in QALYs was primarily a consequence of the fact that patients in the CGA group lived longer. CGA in an ambulatory setting for older people with multi-morbidity results in a cost per QALY of 46,000 EUR compared with usual care, a figure generally considered reasonable in a Swedish healthcare context. A rather simple reorganisation of care for older people with multi-morbidity may therefore cost effectively contribute to meet the needs of this complex patient population. The trial was retrospectively registered in clinicaltrial.gov, NCT01446757 . September, 2011.