The purpose of this randomized, parallel, triple-blinded clinical trial was to compare efficacy and tooth sensitivity (TS) after use of an in-office bleaching agent of 6 % hydrogen peroxide containing nanoparticles of nitrogen-doped titanium oxide (HP6) vs. 35 % hydrogen peroxide (HP35). Forty-eight volunteers were randomly divided either a HP6 or HP35. Two clinical sessions were performed with an interval of 7 days between them for each group. In each session, two consecutive applications of each bleaching agent were performed and activated by a hybrid LED/laser light. Efficacy was determined by color alteration (Delta E), recorded with reflectance spectroscopy. It was assessed at baseline and after the first and second bleaching session. TS was characterized according to occurrence, intensity, duration, and type. Efficacy was analyzed by repeated measures analysis of variance (ANOVA) and post hoc Bonferroni test, and TS was analyzed by means of chi(2) test (alpha = 0.05). For HP35, highest and significant values of Delta E were found after bleaching when compared to HP6 (p = 0.002). However, HP35 showed a significantly higher occurrence of TS than HP6 (p = 0.008). Also, intensity and duration were higher in HP35. The majority of volunteers classified the type experienced in their sensitivity in the form of a "shock." The use of HP6 despite reducing efficacy when compared to an in-office bleaching in higher concentration (35 %) produced less tooth sensitivity. Clinical relevance: In terms of tooth sensitivity, the use of lower concentrations of in-office bleaching should be the first choice, suggesting greater biocompatibility and safety compared to a conventional HP35.