Objective : Although magnetic resonance guided focused ultrasound (MRgFUS) has been used as minimally invasive and effective neurosurgical treatment, it exhibits some limitations, mainly related to acoustic properties of the skull barrier. This study was undertaken to identify skull characteristics that contribute to optimal ultrasonic energy transmission for MRgFUS procedures. Methods : For ex vivo skull experiments, various acoustic fields were measured under different conditions, using five non-embalmed cadaver skulls. For clinical skull analyses, brain computed tomography data of 46 patients who underwent MRgFUS ablations (18 unilateral thalamotomy, nine unilateral pallidotomy, and 19 bilateral capsulotomy) were retrospectively reviewed. Patients' skull factors and sonication parameters were comparatively analyzed with respect to the cadaveric skulls. Results : Skull experiments identified three important factors related skull penetration of ultrasound, including skull density ratio (SDR), skull volume, and incidence angle of the acoustic rays against the skull surface. In clinical results, SDR and skull volume correlated with maximal temperature (Tmax) and energy requirement to achieve Tmax (p<0.05). In addition, considering the incidence angle determined by brain target location, less energy was required to reach Tmax in the central, rather than lateral targets particularly when compared between thalamotomy and capsulotomy (p<0.05). Conclusion : This study reconfirmed previously identified skull factors, including SDR and skull volume, for successful MRgFUS; it identified an additional factor, incidence angle of acoustic rays against the skull surface. To guarantee successful transcranial MRgFUS treatment without suffering these various skull issues, further technical improvements are required. [ABSTRACT FROM AUTHOR]