Introduction: Pharmacotherapy with analgesics and non-steroidal anti-inflammatory drugs has been traditionally used to relief post-operative pain of endodontic treatments. However, due to the side effects reported for these drugs, some efforts have been made to decrease the post-operative pain of the endodontic treatments through laser irradiation. The present study aimed to evaluate the effects of low level laser therapy (LLLT) on the reduction of pain after root canal retreatment. Methods: In this clinical trial, 61 patients requiring endodontic retreatments in posterior teeth were selected. A single visit endodontic retreatment was performed. After biomechanical preparation, low level laser was irradiated to the buccal and lingual mucosa overlying the apices of the target tooth in the experimental group. In the control group patients received placebo laser to eliminate the probable psychological effects of laser. Laser irradiation was done with a single dose of 808 nm wavelength (Whitening Lase II-Laser DMC, Samsung, Korea) with 100 mW power, and dose of 70 J/cm 2 for 80 seconds. Pain severity was recorded before, immediately after and 4, 8, 12, 24 and 48 hours after the treatment by visual analogue scale (VAS). The pain scores were statistically analyzed by chi-square test between 2 groups. The effects of different variables on the post-operative pain experience were also studied by means of Logistic regression. Results: Pain scores decreased significantly through time until 48 hours after treatment. No significant differences were observed between the 2 modalities regarding pain scores at any time. According to regression analysis, pain severity scores were lower in the laser-irradiated specimens than control groups (OR = 5.69); however, this difference was not statistically significant. Consumption of analgesics after the treatment had significant effect in decreasing post-operative pain experience (OR = 56) while factors of age, gender, laser irradiation, pre-treatment pain scores and education level did not. Conclusion: Low level laser irradiation had limited effects to decrease pain associated with the endodontic retreatments in the first and second molars; however, more studies are required to assess the effects of different parameters of low level laser in this regard.