OBJECTIVES: Parkinson's disease (PD) may be caused by an enteric neurotropic pathogen entering the brain through the vagal nerve, a process that may take over 20 years. We investigated the risk of PD in patients who underwent vagotomy, and hypothesized that truncal vagotomy is associated with a protective effect, while super-selective vagotomy has a minor effect. METHODS: We constructed cohorts of all patients in Denmark who underwent vagotomy during 1977-1995 and a matched general population cohort, by linking Danish registries. We used Cox regression to compute hazard ratios (HRs) for PD and corresponding 95% confidence intervals [CIs], adjusting for potential confounders. RESULTS: Risk of PD was decreased in patients who underwent truncal [HR = 0.85, 95% CI= 0.56-1.27; follow-up of >20 years: HR = 0.58, 95% CI: 0.28-1.20] compared to super-selective vagotomy. Risk of PD was also decreased following truncal vagotomy when compared to the general population cohort [overall adjusted HR = 0.85, 95% CI 0.63-1.14; follow-up >20 years, adjusted HR = 0.53 [95% CI: 0.28-0.99]. In patients who underwent super-selective vagotomy, risk of PD was similar to the general population [HR = 1.09, 95% CI: 0.84-1.43; follow-up of >20 years: HR = 1.16, 95% CI: 0.80-1.70]. The statistical precision of the risk estimates was limited. Results were consistent after external adjustment for unmeasured confounding by smoking. INTERPRETATION: Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD. This article is protected by copyright. All rights reserved.