Background <p>Shift work (SW) has been linked to the occurrence of various chronic diseases. However, its potential correlation with gout has not been established. This study aimed to investigate the effects of the SW schedule on incident gout.</p> Methods <p>A total of 281,500 individuals enrolled in the UK Biobank were included in the cohort study. The Cox proportional hazards model was used to investigate the association between SW and incident gout. Additionally, a genetic risk score (GRS) was constructed to assess the joint effects of SW and genetic predisposition on the risk of gout.</p> Results <p>During a 13-year follow-up period, we recorded 4,282 new-onset gout cases. In the current SW analysis, individuals with some night shifts had a 15.1% higher gout risk compared to day workers, which varied by smoking status, chronotype, and obesity status [hazard ratio (HR): 1.151, 95% confidence interval (CI): 1.018–1.301]. The lifetime analysis indicated that individuals with &lt; 5 years of night shifts were more prone to gout than those without night shift exposure, especially when excluding those who developed gout within one year from the baseline (HR: 1.259, 95% CI: 1.027–1.542). An interaction between SW and genetic predisposition was observed, with individuals having both high GRS and some night shifts showing a 218% higher gout risk compared to those with low GRS and day work (HR: 3.18, 95% CI: 2.58–3.92).</p> Conclusions <p>Both current and lifetime SW were associated with an increased gout risk, with genetic predisposition further amplifying this risk. These findings contribute additional evidence to the current understanding of the detrimental effects of SW and provide a novel and important perspective on strategies for the primary prevention of incident gout.</p> Graphical Abstract <p></p>