Adiposity, insufficient physical activity, cigarette smoking, and poor diet have all been related independently to increased chronic disease risk, but their joint impact on overall health remains unclear. In a cohort of 170,672 women and men aged 51-71 years at baseline in 1996/1997 and followed-up through 2009, we investigated the individual and joint impact of four low-risk lifestyle factors: abdominal leanness (waist circumference <88 cm in women and <102 cm in men); recommended physical activity level (30 min or more of moderate exercise at least 5 times per week or 20 min or more of vigorous exercise at least 3 times per week); long-term non-smoking (never-smoker or quit smoking more than 10 years ago); and healthy diet (Mediterranean diet score within the upper two sex-specific quintiles). During 2,126,089 person-years of follow-up, 20,903 participants died. In multivariate Cox models, statistically significant decreased risks of mortality were observed for the low-risk factors abdominal leanness (relative risk (RR) = 0.86; 95 % confidence interval (CI) = 0.83-0.89), physical activity (RR = 0.86; 95 % CI = 0.84-0.89), non-smoking (RR = 0.43; 95 % CI = 0.42-0.45), and healthy diet (RR = 0.86; 95 % CI = 0.83-0.88). The larger the number of low-risk lifestyle factors, the lower was the mortality risk. The RR comparing adherence to all versus none of the factors was 0.27 (95 % CI = 0.25-0.29). We estimate that 33 % (95 % CI = 30-35 %) of deaths in our cohort were premature and could have been avoided if all study participants had adhered to all low-risk factors.