BACKGROUND: There is consistent evidence on the impact of health behaviours on risk of cardiovascular disease (CVD) in European populations. As South Asians in the UK have an excess risk of CVD and coronary heart disease (CHD) compared to Europeans, we investigated whether a similar association between combined health behaviours and risk of CVD and CHD among this high-risk group exists, and estimated the population impact. METHODS AND FINDINGS: In a prospective cohort of 1090 Europeans and 1006 South Asians (40-69 y) without prevalent CVD at baseline (1988-1990), followed up for 21 years to 2011, there were 601 incident CVD events [Europeans n = 255; South Asians n = 346] of which 520 were CHD events [n = 207 and 313 respectively]. Participants scored between 0 to 4 points for a composite score including four baseline healthy behaviours (non-smoker, moderate alcohol intake, physically active, frequent fruit/vegetable intake). Adjusted hazard ratios (95% confidence intervals) for incident CHD in Europeans who had three, two, one, and zero compared to four health behaviours were 1.33 (0.78-2.29), 1.96 (1.15-3.33), 1.36 (0.74-2.48) and 2.45 (1.18-5.10), respectively, p-trend = 0.025. In South Asians, corresponding HRs were 2.88 (1.33-6.24), 2.28 (1.06-4.91), 3.36 (1.53-7.39) and 3.48 (1.38-8.81), p-trend = 0.022. The results were similar for incident CVD; Europeans HR 2.12 (1.14-3.94), p-trend = 0.014; South Asians HR 2.73 (1.20-6.21), p-trend = 0.018. The population attributable fraction in Europeans was 43% for CHD and 28% for CVD. In South Asians it was 63% and 51% respectively. CONCLUSIONS: Lack of adherence to four combined health behaviours was associated with 2 to 3-fold increased risk of incident CVD in Europeans and South Asians. A substantial population impact in the South Asian group indicates important potential for disease prevention in this high-risk group by adherence to healthy behaviours.