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Background: Inadequate efficacy and significant side effect profile makes pharmacological treatment of Parkinson’s disease (PD) tremor challenging. Personalized dosing of botulinum toxin type A (BoNT-A) using tremor analysis has shown efficacy and safety for treating upper limb tremor. This study incorporated a novel, standardized treatment algorithm for determining injection pattern and BoNT-A dosing, customizable by the physician, in PD patients with disabling tremor in one or both arms. Methods: This open-label study included 47 PD participants (25 “De-novo” and 22 “L-dopa”) who received 4 serial BoNT-A treatments with follow-ups at 6 weeks post-treatment over 42 weeks. The treatment algorithm utilized kinematic tremor analysis of each participant’s whole arm tremor and determined the physician’s injection pattern of BoNT-A. Endpoints included changes in angular tremor amplitude, Fahn-Tolosa-Marin (FTM C) tremor scale, Movement Disorder Society-Unified Parkinson’s disease rating scale (MDS-UPDRS) tremor-related score, tremor-related quality of life questionnaire, Likert ratings of perceived weakness, and maximal grip strength. Results: BoNT-A significantly ( p  < 0.05) improved tremor amplitude (41.6%), quality of life (23.0%), UPDRS tremor score (29.6%), and arm function (FTM C; 24.6%) for both treatment cohorts from weeks 6 to 42. Maximum grip strength was reduced between 7.4% and 23.0% at follow-up visits and did not impact activities of daily living. Efficacy was obtained with first injection and remained without adjustment over two serial injection in 45% of participants. Conclusions: This is the first study to use a fully standardized treatment algorithm for personalization of BoNT-A injection patterns for disabling PD tremor over serial treatments. A sustained alleviation of tremor severity and improved arm function and quality of life fulfills an important unmet need for the treatment of PD tremor. This study demonstrated that BoNT-A can be administered as a monotherapy in tremor-dominant PD or as an add-on therapy for refractory PD tremor.