Previous studies have shown that proton pump inhibitors (PPIs) are associated with an increased risk of dementia. However, little is known about the relationship between PPIs use and Parkinson’s disease (PD). This study aimed to examine whether PPI use was associated with an increased risk of developing clinically verified PD. This used data from the Taiwan National Health Insurance Research Database for the period between 1999 and 2011, and patients with PPI use were compared with 1 to 1 propensity score-matched controls by age, sex, cohort entry year, and comorbidity. A multivariate analysis was performed using Cox proportional hazards models to estimate the association between PPI use and PD risk. Subgroup analyses according to sex, age, and comorbidities were also conducted. In total, 56,785 PPI users and 56,785 matched controls were enrolled in this study. In the PPI cohort, 366 patients developed PD during a median follow-up of 5.0 years. The incidence rate of PD was 1.48-fold higher in PPI users than in non-PPI users (90.0 vs 133.2 per 100,000 person-years), with an adjusted hazard ratio of 1.76 (95% confidence interval, 1.48–2.08). In the subgroup analysis, the adjusted risk of PD in the PPI and non-PPI cohorts increased in the subgroups regardless of age, sex, and comorbidities. The results of this retrospective, nationwide, population-based cohort study in Taiwan indicate that PPI use is associated with the risk of PD development. Further mechanistic studies on the effect of PPI on PD are needed.