Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, healthcare professionals were more frequently affected by post-traumatic stress disorder than the general population. The purpose of this historical, prospective study was to determine the influence of occupational stressors and personality traits on the magnitude of post-traumatic stress symptoms in nurses. The secondary objective was to examine the mediating role of protective equipment use on the relationship between exposure to pandemic-related stressors and levels of post-traumatic stress symptoms in nurses. Methods: The study was conducted after the first wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic among nurses working at the University Hospital of Split, Croatia. A total of 380 nurses completed the web-based survey. Among them, 217 (57.1%) worked with COVID-19 patients and 163 (42.9%) worked in non-COVID departments. A quantitative, cross-sectional, descriptive, and comparative design was used. Results: Personality traits (introversion, neuroticism, and openness), along with exposure to work stressors (public criticism, workplace hazards and harms, and work conflicts) and direct exposure to work with patients suffering from SARS-CoV-2 infection, may serve as significant risk factors for the development of post-traumatic stress symptoms (p < 0.05). The use of protective equipment did not alter the effect of exposure to pandemic-related stressors on the amount of trauma experienced during the COVID-19 pandemic. Conclusion: Personality characteristics and levels of work stress are the most important predictors of the development of post-traumatic stress symptoms in nurses who worked during the first wave of the COVID-19 pandemic. Healthcare facilities and their leaders need to make more efforts to provide better psychosocial support services for nurses.