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Background: Cognitive failures are one of the most important causes of patients' unsafe events. Hence, it is necessary to consider individual and cognitive, as well as extra-organizational characteristics. The present study was conducted to investigate the association between personality traits, job stress, work-family conflict and nurses' cognitive failures. Materials and Methods: This descriptive cross-sectional study was conducted among 250 nurses working in three public hospitals in Sari city, Iran, in 2021. The subjects were selected using Stratified Random Sampling. NEO Five-Factor Inventory, Health and Safety Executive (HSE) tool, Work-Family Conflict Scale (WFCS), and Occupational Cognitive Failure Questionnaire (OCFQ) were used to measure personality traits, job stress, work-family conflict, and cognitive Failures, respectively. The data were analyzed in SPSS (ve. 23) and regression analysis with the sequential method was applied. Results: Among 13 studied predictor variables, only extraversion, agreeableness, demand, and role were predictors of cognitive failures. These variables explain 44.1% of the variance of cognitive failure. The β values of neuroticism and conscientiousness to predict cognitive failures were 0.34 and -0.29, respectively (P < 0.001). Although role (β = 0.15, p < 0.001) and demand (β = 0.14, p < 0.001) significantly predict cognitive failure; however, their effect is limited. The results of the study did not provide confirmation for the moderating effect of neuroticism, extraversion, agreeableness, and conscientiousness on the association between work-family conflict, job stress, and cognitive failures. Conclusions: Along with environmental and organizational stress factors, evaluating nurses' personality traits is necessary to control cognitive failures. [ABSTRACT FROM AUTHOR]