Background and Aim: Several dentifrices have shown to be effective in reducing dentine hypersensitivity (DH), but more effective products are needed. The aim of the study was to evaluate the desensitizing efficacy of a new dentifrice based on zinc-carbonate hydroxyapatite (CHA) nanocrystals. Methods and Materials: Using a double-blind, randomized design, the new dentifrice was compared with potassium nitrate/fluoride dentifrice (active control). The participant's DH was evaluated at baseline and after 4 and 8 weeks using airblast (primary outcome), tactile, cold water and subjective tests (secondary outcomes). Results: The final sample consisted of 70 subjects with baseline DH; 36 received the new dentifrice and 34 the control one. Both dentifrices were largely effective; the percentage of score reduction from baseline to 8 weeks was greater than 28% for all tests (and greater than 55% for the cold water test) in both groups. As compared with controls, experimental subjects had a significantly greater improvement in the airblast test score (mean percentage of reduction of 46.0% versus 29.4% in controls) and the subjective test score (47.5% versus 28.1%, respectively), with both differences already being significant after 4 weeks. In contrast, there was no significant difference between groups for either the tactile or cold water tests at any time point and with any outcome. Conclusions: This study documented that the new dentifrice containing zinc-CHA nanocrystals significantly reduced dentinal hypersensitivity after 4 and 8 weeks, supporting its utility in clinical practice.