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Background and aims: Psychologic wellbeing can impact cardiovascular health. We aimed to evaluate the joint association of multiple psychologic wellbeing factors with cardiovascular diseases (CVD) and examine whether this association was modified by genetic susceptibility. Methods: In the UK Biobank, 126,255 participants free of CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) at baseline, who completed a questionnaire on psychological factors, were included. The psychological wellbeing score was calculated by four factors: happiness, life satisfaction, broad depression, and neuroticism. Cox proportional hazard models were used to assess the association between the psychological wellbeing score and CVD risk. Results: During the median follow-up of 11.5 years, 10,815 participants had newly diagnosed CVDs. Low life satisfaction, the presence of depression, and neuroticism score >= 1 were significantly associated with an increased risk of CVD in the multivariable-adjusted model. Through decreasing the psychological wellbeing score, there were significant increasing linear trends in the risk of CVD, CHD, stroke, and HF (all p for trend < 0.001). Participants with the lowest psychological wellbeing score had the highest risk for CVD (HR 1.51, 95% CI 1.42-1.61). Women were more susceptible to worse psychological wellbeing status for CVD than men (p for interaction = 0.009). The associations of the psychological wellbeing score with CVD were consistent across genetic risk (p for interaction >0.05). When considered jointly, participants exposed to high-risk psychological wellbeing and genetic status had a 2.70-fold (95% CI 2.25-3.24) risk for CHD. Conclusions: Joint exposure to multiple psychological wellbeing factors was associated with increased risks of incident CVD in an additive manner, regardless of genetic susceptibility.