OBJECTIVE To investigate the effects of four dentin desensitizers on pain reduction in hypersensitive cervical dentin lesions. METHODS The trial was designed as a randomized, controlled, four-arm, single-masked study. Fifty subjects with at least one hypersensitive lesion in each of the four quadrants were allocated. The requested pre-operative pain, determined as a response to 2-s air-blast (AB) and probe scratching (PS), was ≥5 on a VAS scale, 0 = no through to 10 = worst pain. Randomly each subject received each of the four treatments: MS Coat One F (MSC, Sun Medical, Japan), Nanoseal (NAN, Nishin, Japan), Teethmate Desensitizer (TMD, Kuraray Noritake, Japan) and Gluma Desensitizer PowerGel (GLU, HeraeusKulzer, Germany). The investigator assessed blindly the pain response using the two stimuli and recorded the patients' VAS scores before and immediately after application, after 1 week and after 1, 3 and 6 months. STATISTICAL DATA TREATMENT: ANOVA and post-hoc testing (p ≤ 0.05). RESULTS Forty-nine subjects completed the trial. Pre-operative dentin hypersensitivity (DH) for the groups was not significantly different. All desensitizers reduced DH significantly throughout the 6-months observation. ANOVA revealed significant differences among VAS scores, obtained with the desensitizing agents (p < 0.001). Ranking by post-hoc testing was: MSC > NAN > TMD > GLU (p < 0.05). Upon PS NAN and TMD showed slight but significant regain of sensitivity after 6 months. For GLU PS scores immediately after application and after 6 months were not significantly different, whereas recalls after 1 week, 1 month and 3 months revealed significantly lower scores. CONCLUSIONS The calcium phosphate-based TMD and GLU proved highly effective in reducing sensitivity.