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Adverse medical events (AMEs) are threats to delivery of quality healthcare services, particularly in resource-poor settings such as Ghana. In sub-Saharan Africa, 30% of deaths are attributed to AMEs and a significant proportion of these events are not reported. This study explored personal experiences of nurses with AMEs and the constraints to reporting them. This is a descriptive cross-sectional study among professional (n= 133) and auxiliary (n= 88) nurses in a regional referral hospital in northern Ghana. A test for differences in experiences of professional and auxiliary nurses was done using Wilcoxon Mann-Whitney test. Ordered logistic regression analysis (proportional odds ratio models) and probit regression were used to ascertain the determinants of staff’s knowledge on AMEs and the odds of exposure, respectively. Overall, knowledge and awareness level on AMEs was average (mean = 3.1 out of the five-point Likert scale of 1 = “Very poor” to 5 = “Excellent”). Knowledge levels among professional nurses (mean = 3.2) were relatively higher than those among auxiliary nurses (mean = 3.0), (p= 0.006). The predominant type of AME experienced was wrongful documentation (n= 144), and the least experienced type was wrong transfusion of blood and/or intravenous fluids (IVF) (n= 40). Male staff had higher odds of experiencing medical errors relative to female staff, OR = 2.39 (95% confidence interval (CI), 1.34–4.26). Inadequate logistics was the most perceived cause of AMEs. Knowledge on types of AMEs was significantly associated with gender of the respondents, OR = 1.76 (95% CI, 1.05–2.94); moreover, male staff had higher odds of knowing AME post-exposure action than female staff, OR = 1.75 (95% CI, 1.04–2.93). Knowledge levels of nursing staff on AMEs were generally low, and even though exposures were high they were not reported. There is the need to integrate AME modules into the pre-service and in-service training curricula for nurses to enhance their knowledge on AMEs; reporting registers for AMEs should be made available in clinical sites and staff incentives given to those who report AMEs. Lastly, protocols on AMEs should form part of the quality assurance value chain for health facilities to promote compliance.