OBJECTIVE Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. METHODS The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. RESULTS Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p < 0.0001), 0.206 (p = 0.00219), 0.168 (p = 0.0119), and 0.159 (p = 0.0136), respectively. Third ventricular width, gender, AC-PC distance, and age each account for 44.06% (21.38-65.69%, 95% CI), 20.82% (10.51-35.88%), 21.46% (8.28-37.05%), and 13.66% (2.62-28.64%) of the R2 value, respectively. Effect size calculation was significant for a change in the GPi laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. CONCLUSIONS This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization.