Background and Purpose Parkinson's disease (PD) is a major neurological disorder that requires lifelong treatment, and the combined presence of Helicobacter pylori (H. pylori) infection can increase the required anti-PD medications. We aim to investigate the effect of H. pylon infection in Indian PD patients. Methods We prospectively recruited 36 PD patients from December 2007 to January 2011. All patients underwent a detailed neurological evaluation and serological examination for H. pylori infection. Seropositive and seronegative patients were considered to be the cases and controls, respectively. All patients who were seropositive received triple therapy for 2 weeks. Outcome measures of the mean 'off' Unified Parkinson's Disease Rating Scale (UPDRS)-III score, mean on UPDRS-III score, mean onset time, mean 'on' duration, and mean daily on time were measured at baseline and at a 3-week follow-up. Results H. pylori-IgG positivity was present in 18 (50%) PD patients. The prevalence of men (72.2% vs. 33.3%), mean duration of disease (13.8 vs. 12.5) and mean levodopa equivalent daily dose (824 mg vs. 707 mg) were significantly higher among H. pylon positive patients than in controls (p<0.0001). Controls had a significantly longer 'on duration and daily 'on' time, and better 'on' UPDRS-III scores. Seropositive patients took a significantly longer time to turn 'oil after a levodopa challenge. At the 3-week follow-up, H. pylori eradication significantly improved the mean 'on UPDRS-III score, onset time, 'on' duration, and daily 'on' time. Conclusions H. pylon infection was present in 50% of Indian PD patients. H. pylori seropositivity was associated with a poor response to levodopa and increased medication usage, while eradication therapy was associated with better patient outcomes.