The purpose of this study is to evaluate inter- and intrafractional dose variations resulting from head position deviations for patients treated with the Extend relocatable frame system utilized in hypofractionated Gamma Knife radiosurgery (GKRS). While previous reports characterized the residual setup and intrafraction uncertainties of the system, the dosimetric consequences have not been investigated. A digital gauge was used to measure the head position of 16 consecutive Extend patients (62 fractions) at the time of simulation, before each fraction, and immediately following each fraction. Vector interfraction (difference between simulation and prefraction positions) and intrafraction (difference between postfraction and prefraction positions) shifts in patient position were calculated. Planned dose distributions were shifted by the offset to determine the time-of-treatment dose. Variations in mean and maximum target and organ at risk (OAR) doses as a function of positional shift were evaluated. The mean vector interfraction shift was 0.64 mm (Standard Deviation (SD): 0.25 mm, maximum: 1.17 mm). The mean intrafraction shift was 0.39 mm (SD: 0.25 mm, maximum: 1.44 mm). The mean variation in mean target dose was 0.66% (SD: 1.15%, maximum: 5.77%) for inter-fraction shifts and 0.26% (SD: 0.34%, maximum: 1.85%) for intrafraction shifts. The mean variation in maximum dose to OARs was 7.15% (SD: 5.73%, maximum: 30.59%) for interfraction shifts and 4.07% (SD: 4.22%, maximum: 17.04%) for intrafraction shifts. Linear fitting of the mean variation in maximum dose to OARs as a function of position yielded dose deviations of 10.58%/mm for interfractional shifts and 7.69%/mm for intrafractional shifts. Positional uncertainties when per-forming hypofractionated Gamma Knife radiosurgery with the Extend system are small and comparable to frame-based uncertainties (< 1 mm). However, the steep dose gradient characteristics of GKRS mean that the dosimetric consequences of positional uncertainties should be considered as part of treatment planning. These dose uncertainties should be evaluated in the context of tumor response and OAR tolerance for hypofractionated treatment scenarios where any increase in dose may be tempered by the increased protection hypofractionation provides to normal tissue.