In the healthcare sector, a comprehensive safety culture includes both patient care-related and occupational aspects. In recent years, healthcare studies have demonstrated diverse relationships between aspects of psychosocial working conditions, occupational, and patient safety culture. The aim of this study was to consider and test relevant predictors for staff's perceptions of occupational and patient safety cultures in hospitals and whether there are shared predictors. From two German university hospitals, 381 physicians and 567 nurses completed a questionnaire on psychosocial working conditions, occupational, and patient safety culture. Two regression models with predictors for occupational and patient safety culture were conceptually developed and empirically tested. In the Occupational Safety Culture model, job satisfaction (β = 0.26, ≤ 0.001), work‒privacy conflict (β = -0.19, ≤ 0.001), and patient-related burnout (β = -0.20, ≤ 0.001) were identified as central predictors. Important predictors in the Patient Safety Culture model were management support for patient safety (β = 0.24, ≤ 0.001), supervisor support for patient safety (β = 0.18, ≤ 0.001), and staffing (β = 0.21, ≤ 0.001). The two models mainly resulted in different predictors. However, job satisfaction and leadership seem to play an important role in both models and can be used in the development of a comprehensive management of occupational and patient safety culture.