An economic evaluation was conducted alongside a randomised controlled trial of two lifestyle interventions and a routine care (control) group to assess the cost-effectiveness of a general practice-based lifestyle change program for patients with risk factors for cardiovascular disease. Routine care was the base case comparator because it represents 'current therapy' for cardiovascular disease (CVD). A 'no care' control group was not considered a clinically acceptable alternative to lifestyle interventions. The interventions consisted of an education guide and video for GPs to assess individual patient risk factors and plan a program for risk factor behavior change. Each patient received a risk factor assessment, education materials, a series of videos to watch on lifestyle behaviors and some patients received a self-help booklet. Eighty-two general practitioners were randomised from 75 general practices in Sydney's Western Metropolitan Region to (i) routine care (n = 25), (ii) video group (n = 29) or (iii) video + self help group (n = 28). GPs enrolled patients into the trial who met selection criteria for being at risk of CVD. There were 255 patients in the routine care (control) group, 270 in the video (intervention) group and 232 in the video + self help (intervention) group enrolled in the trial. Outcome measures included patient risk factor status: blood pressure, body mass index, cholesterol and smoking status at entry to trial and after 1 year. Changes in risk factors were used to estimate quality adjusted life years (QALYs) gained. One hundred and thirty patients in the routine care group, 199 in the video group and 155 in the video + self help group remained in the trial at the 12-month review and had complete data. The cost per QALY for males ranged from $AUD152,000 to 204,000. Further analysis suggests that a program targeted at 'high risk' males would cost approximately $30,000 per QALY. The lifestyle interventions had no significant effect on cardiovascular risk factors when compared to routine patient care. There remains insufficient evidence that lifestyle programs conducted in general practices are effective. Resources for general practice-based lifestyle programs may be better spent on high risk patients who are contemplating changes in risk factor behaviours.