Aim: To compare and evaluate the relative analgesic efficacy of low-level single-dose laser and placebo irradiation after the placement of the first arch wire (0.016 inch Ni–Ti wire) at 6, 12, 24, 36, 48, and 72 hours using a visual analog scale (VAS). Materials and methods: Fifteen maxillary arches of 15 patients were selected for the study. All the brackets and molar tubes were bonded and 0.016-inch nickel–titanium wire was inserted and ligated to the bracket using 0.009 inch stainless steel wire. After performing the orthodontic procedures, a low-level laser therapy (LLLT) of wavelength of 980 nm an output of 2 W with an energy density of 40 J/cm² side, and an application dose of 10 J/cm² were applied on the buccal and palatal sides of each tooth for 20 seconds, respectively. The laser beam was placed for the control group on the contralateral side for the same extent of time but in the switched off mode. Patients were asked to assess the pain at home at 6, 12, 24, 36, 48, and 72 hours after irradiation using a VAS. Results: In both the groups, pain increased during the first 12 hours and gradually decreased over the next couple of days. The peak of pain was maximum at 12 hours post irradiation in both the groups. There was a statistically significant (p < 0.005) reduction in pain in the experimental group than the control group at all-time intervals. Conclusion: LLLT significantly reduces orthodontic tooth pain due to the initial archwire activation.