Aim: In the 1990s, several studies noted a large gap in life expectancy between Western and Eastern European countries. It was speculated that this could be explained by environmental pollution, socioeconomic factors, lifestyle and psychosocial stress. A weakness in addressing the issue has been the lack of prospective studies with mortality as end point. Methods: We used the national population registries (between 1996 and 1998) to screen a cohort of 269 55-year-old subjects in Sweden and Estonia. We assessed conventional risk factors, lifestyle and socio-economic factors. A 13-year follow-up regarding all-cause and cardiovascular mortality was done. Results: Smoking and, to a lesser extent, plasma levels of interleukin-6 were significant predictors for CVD and non-CVD mortality in men, but none of the other conventional risk factors reached statistical significance. During the follow-up period, 22 of the 52 male smokers died compared to 8 of the 85 male non-smokers (p<0.01). Ten of the smokers died of CVD compared to three of the non-smokers (p<0.002). In total, only two women died. Conclusions: These data emphasize that smoking prevention is extremely important in preventing premature death. Although smoking prevalence is diminishing, it is still the most important risk factor to treat.