Objective Moral distress is a complex phenomenon experienced by healthcare professionals. This study examined the relationships between key dimensions of Organizational Culture in Healthcare (OCHC)—perceived psychological safety, ethical climate, patient safety—and healthcare professionals’ perception of moral distress.Design Cross-sectional surveySetting Pediatric and adult critical care medicine, and adult hospital medicine healthcare professionals in the United States.Participants Physicians (n = 260), nurses (n = 256), and advanced practice providers (n = 110) participated in the study.Main outcome measures Three dimensions of OCHC were (...) measured using validated questionnaires: Olson’s Hospital Ethical Climate Survey, Agency for Healthcare Research and Quality’s Patient Safety Culture Survey, and Edmondson’s Team Psychological Safety Survey. The perception of moral distress was measured using the Moral Distress Amidst a Pandemic Survey. The hypothesized relationships between various dimensions were tested with structural equation modeling (SEM).Results Adequate model fit was achieved in the SEM: a root-mean-square error of approximation =0.072 (90% CI 0.069 to 0.075), standardized root mean square residual = 0.056, and comparative fit index =0.926. Perceived psychological safety (β= −0.357, p <.001) and patient safety culture (β = −0.428, p<.001) were negatively related to moral distress experience. There was no significant association between ethical climate and moral distress (β = 0.106, p = 0.319). Ethical Climate, however, was highly correlated with Patient Safety Culture (factor correlation= 0.82).Conclusions We used structural equation model to test a theoretical model of multi-dimensional organizational culture and healthcare climate (OCHC) and moral distress.Significant associations were found, supporting mitigating strategies to optimize psychological safety and patient safety culture to address moral distress among healthcare professionals. Future initiatives and studies should account for key dimensions of OCHC with multi-pronged targets to preserve the moral well-being of individuals, teams, and organizations. (shrink)