Contrast-enhanced ultrasound (CE-US)-derived intensity-time gradients (ITGs) can be used for noninvasive monitoring of extracorporeal shock wave sialolithotripsy effects in chronic sialolithiasis-related sialadenitis. Aim of this trial was to further validate CE-US as an independent and quantitative diagnostic tool for sialolithotomy efficacy. In this prospective clinical phase II evidence level c study perfusion in patients (n = 10) with unilateral sialolithiasis of the submandibular gland was quantitatively analyzed by CEUS before and after sialolithotomy comparing with the contralateral disease-free gland. A visual analog scale (VAS) scoring clinical complaints was correlated with CE-US-derived ITGs. Furthermore, ITG ratios reflecting values from the contralateral side and the diseased side were calculated. VAS documented significantly reduced clinical complaints after sialolithotomy indicative of a successful treatment. VAS data significantly correlated with CE-US-derived ITGs. In addition, ITG ratios were significantly increased after sialolithotomy. In conclusion, CE-US-derived ITGs and ITG ratios appear as independent and valid quantitative parameters of sialolithotomy efficacy.