OBJECTIVES: Assess prevalence of medication non-adherence to Parkinson's disease (PD) medications and its association with symptom progression. METHODS: This retrospective, longitudinal cohort study included older adults enrolled continuously for 1 to 5 years in a US Medicare Health Maintenance Organization. The study population was identified using ICD-9 codes (332;332.0) for PD and a claim for at least one filled PD prescription identified using NDC codes. Medication Possession Ratio (MPR) was estimated as proxy for adherence to PD medications, with a threshold of 0.80 indicating adherence. PD symptom progression was defined as increase in prescription strength, addition of another PD medication, an emergency room visit or hospitalization related to PD. Demographic, clinical, and economic variables were extracted from the dataset. Prevalence of non-adherence was calculated over all years and for each year of eligibility. Logistic regression was used to assess relation between medication adherence and PD symptom progression. Sensitivity analyses were conducted for MPR scores less than 0.6, 0.4, and 0.2. RESULTS: The study population (N=470 patient-years) had mean MPR score of 0.49 (±0.38). An average of 66% of study population was not adherent to their PD medications (MPR<0.8 implies non-adherence). Sensitivity analysis with MPR scores less than 0.6, 0.4, and 0.2 indicated an average of 56%, 46% and 35% were not adherent to their PD medications respectively. Subjects adherent to their PD medications (MPR>=0.8) had 67% less odds of experiencing PD symptom progression (OR=0.33;CI:0.12-0.85) compared to people not adherent to PD medications. All subjects with MPR<0.2 experienced PD symptom progression. CONCLUSION: High prevalence of non-adherence to PD medication and its association with PD symptom progression, irrespective of MPR threshold chosen, indicates it is a significant problem. There is a need for mechanisms to improve medication adherence in PD, namely improved patient understanding, simplified treatment regimens and improved tolerability profiles.