Gout is an inflammatory arthritis caused by monosodium urate crystal deposition. Proton pump inhibitors (PPIs) may influence purine metabolism and increase gout risk, but evidence from large-scale real-world data remains limited. We conducted a retrospective cohort study using the Korean National Health Insurance Service database (2002–2019). A control group was generated with inverse probability of treatment weighting (IPTW) based on demographic and clinical factors, and covariate balance was assessed using standardized mean differences. In the crude analysis, PPI use was associated with a higher risk of gout (HR 1.90; 95% CI 1.86–1.94), and this association remained significant after IPTW adjustment (aHR 1.87; 95% CI 1.83–1.92; p<0.001). Kaplan–Meier curves also showed significantly lower gout-free survival in PPI users (log-rank p<0.001). In conclusion, PPI use was significantly associated with increased gout risk in this nationwide cohort study, and further studies are warranted to confirm causality and clarify the underlying mechanisms.