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Background The reasons underlying the loss of efficacy of deep brain stimulation ( DBS) of the thalamic nucleus ventralis intermedius ( VIM- DBS) over time in patients with essential tremor are not well understood. Methods Long-term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM- DBS. The mean ± standard deviation postoperative follow-up was 7.7 ± 3.8 years. At each visit (every 3-6 months), tremor was assessed using the Fahn-Tolosa-Marin tremor rating scale ( FTM- TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [ TEED1sec]). Results The mean reduction in FTM- TRS score was 73.4% at 6 months after VIM- DBS surgery ( P < 0.001) and 50.1% at the last visit ( P < 0.001). The gradual worsening of FTM- TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage ( P = 0.01), pulse width ( P = 0.01), frequency ( P = 0.02), and TEED1sec ( P = 0.008). TEED1sec fit a third-order polynomial curve model throughout the follow-up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM- DBS) was followed by a plateau and a further increase from the seventh year onward. Conclusions The current findings suggest that the waning effect of VIM- DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation. [ABSTRACT FROM AUTHOR]