Introduction: Trauma is a leading cause of death in South Korea. This study aimed to identify the factors associated with secondary traumatic stress of nurses working at regional trauma centers. Methods: A survey-based cross-sectional design was utilized. Data were collected through a structured questionnaire consisting of 5 rating scales and demographic data. Data were analyzed via descriptive statistics, t test, analysis of variance, Pearson's correlation, and multiple regression. Results: One hundred eighty-six nurses participated, and most (84.4%) reported moderate to severe secondary traumatic stress. Exposure to traumatic events averaged 34.33 (SD = 6.25) out of 65 points. Average problem-focused coping was 3.00 (SD = 0.37), emotion-focused coping was 2.57 (SD = 0.26), and dysfunctional coping was 2.17 (SD = 0.41) out of 4 points. Social support from family and friends averaged 5.85 (SD = 0.75), social support from coworkers was 5.78 (SD = 0.83), and social support from supervisors was 4.65 (SD = 1.18) out of 7 points. The factors affecting the respondents' secondary traumatic stress were type D personality (beta = 0.39, P < .001), dysfunctional coping (beta = 0.28, P < .001), problem-focused coping (beta = 0.19, P < .01), desire for job rotation (beta = 0.17, P < .01), and social support from supervisors (beta = -0.12, P = < .05). This regression model was statistically significant and the explanatory power was 46.7% (F = 33.47, P < .001, Adj R-2 = 0.47). Discussion: Along with a personal effort to engage in stress management programs, administrators, managers, and supervisors should prioritize developing practical strategies for reducing secondary traumatic stress of nurses.