Introduction; Intensity Modulated Radiation Therapy (IMRT) requires exquisite set-up reproducibility for precise RT dose delivery in head and neck cancer (HNC) treatment. Set-up reproducibility is commonly ensured with the utilization of thermoplastic immobilization mask systems, daily image guidance, and positional corrections made by linear accelerator treatment tables. This study compared two thermoplastic mask systems in set-up reproducibility and dosimetric impact using a daily volumetric image guided 4 degree of freedom (DOF) table. Methods and Materials; A retrospective study of 22 patients, eleven in each mask system A and B, was performed to compare set-up reproducibility and dosimetric impact. Mean absolute positional shifts in 6 DOF, including mediolateral (ML), superior-inferior (SI), antero-posterior (AP), pitch, yaw, and roll were compared between mask systems utilizing mixed effects linear regression. Mean percent errors in planned versus recalculated RT doses for 27 HN dose parameters (9 planned target volume (PTV) and 18 normal tissue) were compared using two-sample t-tests. Results; There were no statistically significant differences in clinical characteristics thought to impact daily RT set-up reproducibility between mask groups A and B. The mean absolute positional shifts in ML, SI, AP, pitch, yaw, roll for mask group A was 1.51 mm, 2.06 mm, 6.11 mm, 0.43°, 0.39°, 0.27°, respectively, and for mask group B was 1.43 mm, 1.93 mm, 6.48 mm, 0.33°, 0.47°, 0.29°, respectively. There were no statistically significant differences between groups. The range of mean percent errors in dose parameters evaluated was less than +/−4% between planned and recalculated. No differences were seen in mean percent errors for any of the 27 HN dosimetric parameters evaluated between groups. Conclusions; Set-up reproducibility and dosimetric impact after 4 DOF volumetric image guidance based corrections were minimal and similar between thermoplastic mask systems.