Objectives: To determine if a whole-system approach to self-management in inflammatory bowel disease (IBD), using a guidebook developed with patients and physicians trained in patient-centred care, leads to cost-effective use of health system resources. Methods: Cost-effectiveness analysis over a one-year time horizon comparing the whole systems self-management approach to treatment with usual treatment. Nineteen hospitals in the northwest England were randomized to the intervention or to be controls; 651 patients (285 at intervention sites and 366 at control sites) with established IBD were included. The economic evaluation related differential health service costs, from a UK NHS perspective, to differences in quality-adjusted life years (QALYs) based on patients' responses to the EQ-5D. Results: The intervention was associated with a mean reduction in costs of £148 per patient and a small mean reduction in QALYs of 0.00022 per patient compared with the control group. This resulted in an incremental cost per QALY gained of £676,417 for treatment as usual and a probability of around 63% that the whole-system approach to self-management is cost-effective, assuming a willingness to pay up to £30,000 for an additional QALY. Conclusions: Although there is uncertainty associated with these estimates, more widespread use of this method in chronic disease management seems likely to reduce health care costs without evidence of adverse effect on patient outcomes.