This study aimed to identify the relationship between nurses' job autonomy, perceptions of organizational policy, and safety performance by identifying the safety performance predictors of nurses working in acute health care settings in South Korea. Using data from a structured questionnaire, this cross-sectional descriptive study assessed the relationship between nurses' job autonomy, perceptions of organizational policy, and safety performance. In 2016, of the 290 nurses from nine acute care hospitals in South Korea invited to participate in the survey, 254 successfully did. Using cross-sectional data, characteristics of hospitals and nurses were analysed with t tests, one-way analyses of variance, Pearson correlations, and regression models. On a scale of one to five, the mean job autonomy was 3.37, mean perceptions of organizational policy was 3.09, and mean safety performance was 3.75. Statistically significant positive correlations were found among job autonomy, perceptions of organizational policy, and safety performance. Multiple regression results found 44% of the variation in safety performance explained by job autonomy, length of employment, and perceptions of organizational policy. Job autonomy and perceptions of organizational policy were positively related to safety performance. Hospital executives and nurse managers should work to enhance job autonomy and positive perceptions of organizational policy, to contribute to improving patient safety.