Background The study aimed to examine whether after confounding by possible socio-demographic and other risk factors, psychological well-being is independently associated with reduced all-cause and cardiovascular mortality. Methods Initial data were collected within the framework of the international project HAPIEE in 2006–2008. A random sample of 7115 individuals aged 45–72 years was screened. Deaths were evaluated by death register of Kaunas city (Lithuania) in a follow-up study till 2016. Psychological well-being was evaluated by a CASP-12 questionnaire. Socio-demographic, lifestyle, biologic factors and depressive symptoms were evaluated. Results Age-adjusted survival curves revealed that psychological well-being predicts longevity in men and women ( p  < 0.001). After adjustment for many possible confounders psychological well-being was independently associated with all-cause mortality in men (HR 0.77; 95% CI 0.62–0.94) and women (HR 0.73; 95% CI 0.56–0.96). However, psychological well-being association with cardiovascular mortality attained statistical significance only in the women’s group (HR 0.53; 95% CI 0.33–0.87), but not in men (HR 0.98; 95% CI 0.72–1.33). Conclusions Psychological well-being is an important predictor of longevity, controlling well-recognized risk factors such as age, education, cardiovascular diseases, social status, marital status, lifestyle and biological factors and depressive symptoms. Positive psychological well-being should be taken into account when screening older people to prevent negative health outcomes.