OBJECTIVES: To assess increased all-cause costs incurred by patients experiencing various adverse effects (AEs) associated with Parkinson’s disease (PD) and its treatments in a large, real-world population. METHODS: A retrospective analysis was conducted using the MarketScan database, an employer-based source of inpatient, outpatient, and pharmacy claims of >30 million lives from 2000–2011. Inclusion criteria were: ≥1 PD diagnosis (ICD-9-CM 332.0) and ≥1 anti-PD treatment claim (levodopa, dopamine agonist, anticholinergic, MAOB-inhibitor, COMT-inhibitor, or amantadine) during 2000-2011. Separate case/control cohort analyses were conducted for each AE (dyskinesia, orthostatic hypotension, secondary hypertension, nausea, edema, neuroleptic/serotonin syndrome, impulse control disorder, somnolence, sleep attacks, hallucinations, psychoses) and for all AEs combined. Index dates were assigned as first AE diagnosis for cases and first anti-PD prescription claim for controls. Patients were enrolled pre-index for ≥6 months and post-index for ≥12 months. All-cause costs were aggregated over 12 months post-index. Costs (2012 $) were adjusted using GLM models with covariates for demographics and pre-index comorbidities. RESULTS: A total of 71,883 patients met the inclusion criteria, 45,719 with ≥1 AE (mean[SD] age: 74.9[11.0] years, 55% male) and 26,164 with no AEs (mean[SD] age: 75.0[10.9] years, 59% male). Among patients with ≥1 AE, mean total all-cause costs per patient were substantially higher as compared with controls ($23,568 vs. $13,633; p<0.001), with the difference driven roughly equally by incremental inpatient and outpatient costs of $4,398 and $5,031, respectively (both p<0.001). For all AEs individually, patients experiencing the AE had substantially higher mean all-cause costs, with the largest differences for orthostatic hypotension ($30,551 vs. $17,635), hallucinations ($30,822 vs. $17,843), and nausea ($32,865 vs. $16,456) (all p<0.001). CONCLUSIONS: PD patients experiencing AEs incur substantially higher costs as compared with patients without AEs. These data may be useful in evaluating the cost-effectiveness of new PD therapies with more favorable AE profiles.