Background: Posttraumatic Stress Disorder (PTSD) is a debilitating mental health disorder. Certain drugs, such as morphine and nitrous oxide gas (N₂O), are administered to individuals who just experienced a traumatic event (e.g., soldiers, injured civilians). It is therefore crucial to understand if they incidentally affect PTSD symptom development. Furthermore, such observations could pave the way for the development of pharmacological prevention strategies of PTSD. Methods: In this prospective population-based cohort study (n = 2,070), we examined the relationship between morphine or N₂O administration during childbirth, and subsequent childbirth-related PTSD symptoms at eight weeks postpartum. Pain during labour, prior PTSD symptoms, and birth medical severity were included as covariates in the analyses. Results: In women who developed PTSD symptoms, N₂O administration during childbirth predicted reduced PTSD symptom severity (p <.001, small to medium effect size). A similar tendency was observed for morphine, but was not significant (p <.065, null to small effect size). Both drugs predicted increased PTSD symptoms when combined with severe pain during labour. Limitations: This study was observational, thus drug administration was not randomised. Additionally, PTSD symptoms were self-reported. Conclusions: Peritraumatic N₂O administration may reduce subsequent PTSD symptom severity and thus be a potential avenue for PTSD secondary prevention. This might also be the case for morphine. However, the role of severe peritraumatic pain in context of drug administration deserves further investigation.