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Background: The results from thalamic deep brain stimulation (DBS) for atypical tremor syndromes including tremor from multiple sclerosis (MS) and stroke are often disappointing. Three recent case reports have suggested that simultaneous stimulation of multiple thalamic targets can result in sustained improvement in such cases. Methods: We analyzed the effectiveness of multiple target DBS in one patient with MS-related tremor and another with poststroke Holmes’ tremor. Results: In the patient with MS tremor, we implanted bilateral ventralis intermedius (V.im.) and ventralis oralis anterior (V.o.a.) thalamic electrodes; this patient had significant tremor improvement with stimulation of either V.im. or V.o.a. targets; however, we did not observe additive effects with simultaneous stimulation. In our patient with a poststroke Holmes’ tremor, we implanted DBS electrodes in unilateral V.im., V.o.a., and the globus pallidus internus (Gpi); this patient had moderate tremor reduction with Gpi stimulation alone; neither V.im. nor V.o.a. stimulation provided additional benefit. Conclusion: In one patient with MS tremor, simultaneous V.im. and V.o.a. stimulation was not superior to V.im. or V.o.a. stimulation alone. In one case of Holmes’ tremor, Gpi stimulation was a useful alternative to thalamic stimulation.