Bleaching-induced tooth sensitivity (TS) is highly prevalent. Objective: This study aimed to determine if the combination of opioids and nonopioids analgesics (Tylex) may provide a better analgesic effect. Method: A triple-blind, parallel, randomized two-center clinical trial was conducted with 105 healthy patients who received either a placebo or a combination of acetaminophen/codeine. The first dose of Tylex 30 mg (acetaminophen 500 mg/codeine 30 mg) or placebo was administered one hour before the in-office bleaching (35% hydrogen peroxide), and extra doses were administered every six hours for 48 hours. The TS was recorded using a visual analog scale of 0 to 10 and a numeric rating scale of 0 to 4 in different periods: during bleaching, one hour up to 24 hours, and 24 hours up to 48 hours postbleaching. The color was measured before and one month after dental bleaching with a visual shade guide (Vita Classical), Vita Bleachedguide 3D-MASTER, and the spectrophotometer Vita Easyshade. The absolute risk of TS was evaluated using the Fisher exact test. Data of TS intensity with numeric rating scale of the two groups were compared with the Mann-Whitney U-test and the Friedman test, while data from the visual analog scale were evaluated by two-way repeated measures analysis of variance and the Tukey test for pairwise comparison. The color changes between groups were compared using the Student t-test (α=0.05). Results: No significant differences between the groups were observed in the risk and intensity of TS. The overall absolute risk of TS was approximately 96%. No significant differences between groups were observed in terms of color change (p>0.05) for any scale. Conclusion: The use of an acetaminophen/codeine combination prior to in-office bleaching does not reduce the risk and intensity of bleaching-induced TS.