Purpose: This study was investigated the mediating effect of coping behaviors in the relationship between the second victim experiences after patient safety incidents and the nursing practice changes. Methods: A cross-sectional survey was performed using structured questionnaires. Participants were 218 clinical nurses in general tertiary hospitals in South Korea. Data were collected through an online survey and snowball sampling from August 11 to September 6 2020. Data were analyzed using SPSS 23.0 program. A mediation analysis was performed using multiple regression and a simple mediation model applying the PROCESS macro with 95% bias-corrected bootstrap confidence interval. Results: The mean scores of second victim experiences was 3.41/5. Approach coping (β = .55, p < .001) and the avoidant coping (β = - .23, p = .001) showed mediation effects in the relationship between second victim experiences and constructive change in nursing practice. Avoidant coping (β = .29, p < .001) showed a mediation effect in the relationship between second victim experiences and defensive change in nursing practice. Conclusion: Coping behaviors has a mediating effect on the relationship between second victim experiences and nursing practice changes. To ensure that nurses do not experience second victim, medical institutions should have a culture of patient safety that employs a systematic approach rather than blame individuals. They also need to develop strategies that enhance approach coping and reducing avoidant coping to induce nurses’ constructive practice changes in clinical nurses in experiencing second victims due to patient safety incidents.