Moral injury (i.e., perpetrating, witnessing, failing to prevent, or being a victim of acts that transgress one's moral beliefs, values, or ethics) has largely been studied in military‐connected populations and is associated with a range of adverse psychological sequelae. Emerging literature suggests that healthcare workers also experience moral injury, particularly in the context of the ongoing COVID‐19 pandemic. However, it is not known if moral injury contributes to substance use among healthcare workers or whether these effects might differ by gender, race/ethnicity, or occupational level. In March 2022, we collected self‐reported pilot data from a diverse sample of US healthcare workers (N = 200) We examined the cross‐sectional relationships between moral injury and several measures of substance use (i.e., current non‐medical use of prescription drugs [NMUPD], current cannabis use, current use of other illicit drugs, and hazardous drinking) using separate logistic regression models. Next, we used separate interaction models to examine if any of these relations differed by gender, race/ethnicity, or occupational level. In main effects models, healthcare workers reporting greater moral injury had greater odds of current NMUPD (adjusted odds ratio (aOR) = 1.07; p < 0.001), current use of other illicit drugs (aOR = 1.09; p < 0.01), and hazardous drinking (aOR = 1.07; p < 0.01). These relations did not differ by race/ethnicity or occupational level (ps > 0.05); however, men were more likely to report current NMUPD and hazardous drinking (ps < 0.05) in the presence of high moral injury than women healthcare workers. Our findings suggest that healthcare workers experience substantial distress related to morally injurious events, which may affect their likelihood of NMUPD, cannabis use, use of other illicit drugs, and hazardous drinking, and that men in healthcare may be particularly at risk. Healthcare organizations should address systemic issues driving moral injury (e.g., resource shortages, lack of psychosocial support) to prevent substance‐related harms among healthcare workers.