OBJECTIVE: To estimate the cost effectiveness of four different lifestyle interventions for knee pain. DESIGN: Cost utility analysis of randomised controlled trial. SETTING: Five general practices in the United Kingdom. PARTICIPANTS: 389 adults aged > or = 45 with self reported knee pain and body mass index (BMI) > or = 28. INTERVENTIONS: Dietary intervention plus quadriceps strengthening exercises, dietary intervention, quadriceps strengthening exercises, and leaflet provision. Participants received home visits over a two year period. MAIN OUTCOME MEASURE: Incremental cost per quality adjusted life year (QALY) gained over two years from a health service perspective. RESULTS: Advice leaflet was associated with a mean change in cost of -31 pounds sterling, and a mean QALY gain of 0.085. Both strengthening exercises and dietary intervention were more effective (0.090 and 0.133 mean QALY gain, respectively) but were not cost effective. Dietary intervention plus strengthening exercises had a mean cost of 647 pounds sterling and a mean QALY gain of 0.147 and was estimated to have an incremental cost of 10,469 pounds sterling per QALY gain (relative to leaflet provision), and a 23.1% probability of being cost effective at a 20,000 pounds sterling/QALY threshold. CONCLUSION: Dietary intervention plus strengthening exercises was estimated to be cost effective for individuals with knee pain, but with a large level of uncertainty. TRIAL REGISTRATION: ISRCTN93206785.