Background: Extensive scientific and clinical evidence indicates that continuous delivery of a dopaminergic agent is associated with significant reduction in motor complications compared with intermittent oral dosing with the same agent. There has been an intensive effort to develop a method of providing continuous plasma levels of a dopaminergic agent that avoids the need for surgical therapy or an infusion system. Studies in MPTP-treated monkeys demonstrate that once-weekly injections of polymer-linked rotigotine provide continuous plasma levels and antiparkinsonian benefits. Methods: We performed a multicenter open-label, multiple-ascending-dose-ranging cohort study to evaluate the safety, tolerability, and pharmacokinetics of polymer-linked rotigotine in PD patients. Results: A total of 19 patients were evaluated in 4 cohorts in doses of 20 50, 100, and 200 mg of polymer-linked rotigotine, administered subcutaneously once weekly. The study demonstrated remarkably stable dose-related plasma levels of total and free rotigotine with no accumulation or dumping. Treatment was generally safe and well tolerated. One subject in the 50-mg group discontinued because of hives, which cleared rapidly with antihistamine treatment. Conclusions: This study demonstrates that once-a-week subcutaneous administration of polymer-linked rotigotine provides relatively constant plasma levels of rotigotine and is safe and well tolerated. These findings suggest that this convenient method of delivery of rotigotine has the potential to treat or prevent motor complications in PD patients without the need for a surgical procedure or an infusion system. This approach may also prove applicable to other agents such as apomorphine that can be linked to this polymer © 2020 International Parkinson and Movement Disorder Society.