Upper limb tremor is a disabling condition common to many diseases, and there is no standardized therapy for it. In this study, we report our experience on botulinum toxin (BoNT) therapy as optional treatment for drug-refractory tremor, focusing on tremor pattern selection and injection strategy. We retrospectively evaluated 19 patients with upper limb tremor, 14 of them with proximal-dominant pattern; in 9 cases injection was electromyography (EMG)-guided. Clinical severity was assessed before and after treatment with The Essential Tremor Rating Assessment Scale (TETRAS). We observed a significant reduction of severity at the TETRAS; within the 58% of patients who perceived a subjective satisfaction after the treatment, many received EMG-guided treatment. Regarding the muscles selected as injection targets in satisfied and unsatisfied patients, the teres major and the infraspinatus were significantly more frequently selected in satisfied patients than in unsatisfied patients. No significant side effects were reported. Hence, BoNT treatment could represent an effective therapeutic strategy for patients with proximal upper limb tremor, in particular if injection procedure is EMG-guided and directed to specific muscle targets, especially teres major and infraspinatus.