Background: Major hallmarks in the pathophysiology of Parkinson disease are cellular energy depletion and oxidative stress leading to cellular dysfunction and death. Coenzyme Q₁₀ (CoQ₁₀) is an electron acceptor bridging mitochondrial complexes I and II/III and a potent antioxidant that consistently partially recovers the function of dopaminergic neurons. Objective: To determine whether nanoparticular CoQ₁₀ is safe and displays symptomatic effects in patients with midstage Parkinson disease without motor fluctuations. Design: Multicenter, randomized, double-blind, placebo-controlled, stratified, parallel-group, single-dose trial. Setting: Academic and nonacademic movement disorder clinics. Patients: One hundred thirty-one patients with Parkinson disease without motor fluctuations and a stable antiparkinsonian treatment. Intervention: Random assignment to placebo or nanoparticular CoQ₁₀ (100 mg 3 times a day) for a treatment period of 3 months. Stratification criterion was levodopa treatment. Main Outcome Measure: The subjects underwent evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS) at each visit on a monthly basis. The primary outcome variable was the change of thesumscore of the UPDRS parts II and III between the baseline and 3-month visits. Results: One hundred thirty-one subjects were randomized according to the protocol. The mean changes of the sum UPDRS parts II/III score were -3.69 for the placebo group and -3.33 for the CoQ₁₀ group (P=.82). Statistical analysis according to the stratification did not result in significant changes of the primary outcome variable. No secondary outcome measure showed a significant change between the placebo group and the CoQ ₁₀ group. The frequency and quality of adverse events were similar in both treatment groups. Conclusions: Nanoparticular CoQ₁₀ at a dosage of 300 mg/d is safe and well tolerated and leads to plasma levels similar to 1200 mg/d of standard formulations. Add-on CoQ₁₀ does not display symptomatic effects in midstage Parkinson disease. Trial Registration: clinicaltrials.gov Identifier: NCT00180037