Objectives: The costs of comprehensive cardiac rehabilitation are established and compared to the corresponding costs of usual care. The effect on health-related quality of life is analyzed.Methods: An unprecedented and very detailed cost assessment was carried out, as no guidelines existed for the situation at hand. Due to challenging circumstances, the cost assessment turned out to be ex-post and top-down.Results: Cost per treatment sequence is estimated to be approximately €976, whereas the incremental cost (compared with usual care) is approximately €682. The cost estimate is uncertain and may be as high as €1.877.Conclusions: Comprehensive cardiac rehabilitation is more costly than usual care, and the higher costs are not outweighed by a quality of life gain. Comprehensive cardiac rehabilitation is, therefore, not cost-effective.