The aim of this paper is to describe the intra-operative findings and surgical results of the first application of 3D high-definition (HD) endoscopicsupport to the trans-oral surgical treatment of five patients with deep hilo-parenchymal sub-mandibular stones who underwent clinicaland ultrasonographic (US) follow-up examinations at one month after the procedure. Five patients undergoing 2D-HD video-assistedtransoral surgery for the same condition were used as controls. The results were classified as successful (US - demonstrated complete clearance)or unsuccessful (US - demonstrated total or partial persistence). Visual analogue scales (VAS) were used post-surgically to evaluatethe sharpness and brightness of the 2D and 3D images on the screen and stereoscopic depth perception (SDP) of the 3D-HD endoscope.Successful stone removal and significant subjective improvement (lack of obstructive symptoms) was obtained in all but one of the patientsin the 3D group, in whom the one-month US evaluation revealed a residual 3 mm asymptomatic hilo-parenchymal stone that was successfullytreated by sialendoscopy-assisted intra-corporeal laser lithotripsy. Wharton’s duct and the lingual nerve were identified and preservedin all cases. The mean 3D-HD VAS results were brightness 7 (range 6-8), sharpness 7.8 (range 7-9) and SDP 8.2 (range 8-9); the mean2D-HD results were brightness 7.8 (range 7-9) and sharpness 7 (range 7-8). Our findings confirm the safety and efficacy of conservativetransoral surgical treatment of hilo-parenchymal sub-mandibular stones. From a surgeon’s perspective, 3D-HD guided exploration of theoral floor seems to provide a better view of Wharton’s duct and the lingual nerve, especially near the sub-mandibular parenchyma. The3D-HD video-assisted transoral removal of deep hilo-parenchymal sub-mandibular stones can therefore be considered a useful new meansof preserving the function of an obstructed salivary gland.