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Purpose: The purpose of this study is to determine whether having an optimistic outlook on life decreases the risk of developing incident stroke.Methods: Participants who developed incident stroke in Americans’ Changing Lives study, and participants who did not develop incident stroke (dependent variable) in were compared for demographics, baseline characteristics, comorbidities, and optimistic outlook on life. Numbers and proportions of respondents in both groups were reported for all categorical variables, while mean and standard deviation were reported for age. All statistically significant variables from the above analyses were entered into a logistic regression analysis to ascertain the association between optimistic outlook on life and stroke.Results: Of the 98,577,928 participants, 73,040,055 did not have stroke at baseline. There were 599,190 who developed incident stroke and 1,104,751 who did not develop incident stroke. The mean age (standard deviation) was lower in those who developed incident stroke compared to those who did not [45.9 (13.8) vs. 46.4 (9.9) p<.0001], and participants with an optimistic outlook on life, were 0.20 times less likely to develop stroke as those who did not have an optimistic outlook on life [OR (Odds ratio) 0.20 95% CI (95% confidence interval) 0.20,0.21], after adjusting for confounders.Conclusions: People who have an optimistic outlook on life are less likely to develop incident stroke. The protective value of optimism lends credence to the value of targeting unconventional risk factors in stroke prevention.