Poor psychological health is associated with Takotsubo cardiomyopathy, cardiac syndrome X, coronary microcirculatory dysfunction, peripheral artery disease, or spontaneous coronary artery dissection. Data regarding pessimism, cardiovascular disease (CVD) events and mortality and all-cause mortality remained inconclusive. This systematic review and meta-analysis aim to provide an overview of the association between pessimism, CVD outcomes and mortality. A systematic search of electronic databases was conducted from inception through July 2022 for studies evaluating pessimism and adverse outcomes. A total of 17 studies published between 1966 and July 2022 met our inclusion criteria, for a total of 232,533 individuals. Pooled hazard ratios were calculated in random-effects meta-analyses. Based on pooled analysis of adjusted HRs, pessimism was associated with adjusted HR of 1.13 (95% CI 1.07-1.19) for all-cause mortality with minimal heterogeneity (I2 = 28.5%). Based on pooled analysis of adjusted HRs, pessimism was associated with adjusted HR of 1.30 (95% CI 0.43-3.95) for CHD mortality, adjusted HR of 1.41 (95% CI 1.05-1.91) for CVD mortality, and adjusted HR of 1.43 (95% CI 0.64-3.16) for stroke. In conclusion, pessimism seems to be significantly associated with a higher risk for and poorer outcomes from CVD events than optimistic styles. There are genetic and other bases for these life approaches, but behavioral, cognitive and meditative interventions can modify patients' level of pessimism, hopefully leading to better medical outcomes. Testing this theory would yield highly useful and practical data for clinical care.