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BACKGROUND Overcoming existing access barriers is crucial for better-specialized health care of patients with Parkinson's disease (PD). OBJECTIVE The aim of the study was to compare the access and visit quality/acceptability between in-office and virtual telemedicine visits. METHODS This was an international, randomized, case-control, prospective, observational study. Patients were randomly assigned either to the control group (in-person/in-office visits at baseline, 3, 6, 9, and 12 months) or to the study group (in-office visits at baseline, 6, and 12 months, and telemedicine visits at 3 and 9 months). Telemedicine visits were conducted using videoconferencing apps that were readily accessible to the patient/caregivers. Outcomes were feasibility, usability, and the noninferiority of telemedicine compared to in-office visits in PD patients regarding clinical progression and initiation of pharmacological/nonpharmacological treatments over 1-year follow-up. RESULTS We included 209 PD patients from 6 countries (Nigeria, Spain, Saudi Arabia, South Korea, Egypt, and Uruguay), mean age 64.9 ± 12.2 years, 59% males, median Hoehn & Yahr stage 2 (1-4). Overall, disease progression (MDS-Unified PD rating scale), quality of life (PD-Quality of life 39-items) scores, and therapeutic changes were similar in both groups. After 1 year, 124 patients 48.3%, (control group) and 52.1% (study group) completed the visits (P = 0.52), with a similar high rate of patient's satisfaction with the visits (P = 0.57). CONCLUSIONS This study represents real-world telemedicine practice in different world regions using a telemedicine approach complementary to in-person visits. Based on these results, feasibility, clinical management, PD disease progression, and patient's quality of life are similar when using telemedicine versus in-office visits. Future research should explore ways to integrate different healthcare technologies for long-term PD management.