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. 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). 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. 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.