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Objective To investigate the associations between shift work and the risk of psychotropic medication prescriptions (PMPs), specifically, neuroleptics, sedatives, hypnotics, and antidepressants, among nursing staff in Region Stockholm.Material and Methods Using register-based data, 32,275 nurses and nursing assistants employed for at least one year by Region Stockholm between 2008 and 2019 were included. Exposures were obtained from a computerised employee register while PMPs were obtained from a pharmaceutical register. With one year follow-up, discrete time proportional hazard models were used to estimate hazard ratios (HR), adjusting for covariates.Results Increased risks of PMPs were recorded among those who only worked night shifts (HR 1.14, 95% CI 1.08–1.20) compared to those who worked day shifts, and those who worked night shift frequently (>121 times) compared to those who never worked nights (HR 1.04, 95% CI 1.02–1.05) in the preceding year. Among night workers, increased risks were recorded for those who worked 3 or more consecutive nights 13-21 times and >21 times (HR 1.04, 95% CI 1.02–1.07, and HR 1.08, 95% CI 1.06–1.11 respectively) compared to those with none. Night workers who had quick returns from night shift (<28hrs) of >69 times recorded an increased risk compared to those who had 0-9 times (HR 1.06, 95% CI 1.04–1.09). Lastly, decreased risks were recorded for quick returns from afternoon (<11hrs) 18-32 times, 33-49 times, and >49 times (HR 0.94, 95% CI 0.92–0.95, HR 0.94, 95% CI 0.92–0.95, and HR 0.98, 95% CI 0.96–0.99 respectively) compared to day shift only.Conclusion Exclusive night work is associated with a small but statistically significant increase in risk of PMPs compared to day work. However, day work only is associated with increased risks compared to afternoon shift.