Objective This randomized clinical trial evaluated the effectiveness and tooth sensitivity (TS) of 37.5% hydrogen peroxide (37.5HP) in‐office bleaching with reduced protocol. Materials and methods Forty participants with shade mean C2 or darker for the six maxillary anterior teeth were randomly allocated into two treatment groups (n = 20): two (37.5HP2) or three (37.5HP3) 8 min applications/clinical session. Three clinical sessions were performed with a 1 week interval. Color evaluations were done with a spectrophotometer at baseline and 1 week post‐bleaching. TS was measured during and up to 48 h after bleaching using a five‐point numeric rating scale. Color change was evaluated by Student's t‐test for independent samples. The absolute risk and intensity of TS were analyzed by Fisher's and Mann–Whitney/Friedman tests (p < 0.05). Result Both treatment groups resulted in a significant tooth whitening 1 week post‐bleaching (p < 0.001). There were no significant differences between 37.5HP2 and 37.5HP3 for ΔE*ab, ΔE00 and ∆WID. Also, there were not differences between groups regarding high absolute risk (p = 1.0) and low intensity of TS at all time assessments (p > 0.7). Conclusions The in‐office bleaching with two 37.5% HP applications produced the same whitening degree, risk and intensity of TS to that performed with three gel applications. Clinical significance Clinicians should opt to use a neutral 37.5% HP in‐office bleaching gel for two 8 min applications/clinical session because produces the same whitening effectiveness, risk and low intensity of TS as the protocol proposed by manufacturer (three 8 min applications).