Objective <p>Dentin hypersensitivity (DH) is a common clinical condition characterized by transient, sharp pain arising from exposed dentinal tubules in response to external stimuli. The aim of this study was to evaluate and compare the efficacy of two toothpaste formulations: one containing 5% potassium nitrate alone and another combining 5% potassium nitrate with 2.18% aluminum lactate.</p> Materials and methods <p>This was a parallel-group, randomized, double-blind, negative-control trial with 127 participants. Participants were randomly assigned to three groups (two test and one placebo). The Dentin Sensitivity Index (DSI) was assessed under tactile and air stimulation at baseline, immediately after brushing, and at 2 weeks, 4 weeks, 4 weeks plus 24 h, and 8 weeks.</p> Results <p>Compared with baseline, both test groups showed statistically significant reductions in DSI for both tactile and air stimulation at all time points immediately after use. From 2 weeks onward, the DSI of both test groups was significantly lower than that of the placebo group at all evaluated time points. Furthermore, the toothpaste containing 5% potassium nitrate combined with 2.18% aluminum lactate exhibited a greater effect than the potassium nitrate alone at specific time points: 4 weeks for air stimulation, 4 weeks plus 24 h for tactile stimulation, and 8 weeks for both types of stimulation.</p> Conclusions <p>Both toothpaste formulations—5% potassium nitrate alone and 5% potassium nitrate combined with 2.18% aluminum lactate—demonstrated significant efficacy in reducing dentin hypersensitivity, with the combination showing greater improvement at several time points.</p> Clinical trial registration <p>Trial registration: ISRCTN80733222.</p>