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The aim of this study was to evaluate the effect of low-level laser irradiation applied at 3-week intervals on orthodontic tooth movement and pain associated with orthodontic tooth movement using self-ligating brackets.Twenty-two patients (11 male, 11 female; mean age, 19.8 ± 3.1 years) with Angle Class II Division 1 malocclusion were recruited for this split-mouth clinical trial; they required extraction of maxillary first premolars bilaterally. After leveling and alignment with self-ligating brackets (SmartClip SL3; 3M Unitek, St Paul, Minn), a 150-g force was applied to retract the canines bilaterally using 6-mm nickel-titanium closed-coil springs on 0.019 x 0.025-in stainless steel archwires. A gallium-aluminum-arsenic diode laser (iLas; Biolase, Irvine, Calif) with a wavelength of 940 nm in a continuous mode (energy density, 7.5 J/cm2/point; diameter of optical fiber tip, 0.04 cm2) was applied at 5 points buccally and palatally around the canine roots on the experimental side; the other side was designated as the placebo. Laser irradiation was applied at baseline and then repeated after 3 weeks for 2 more consecutive follow-up visits. Questionnaires based on the numeric rating scale were given to the patients to record their pain intensity for 1 week. Impressions were made at each visit before the application of irradiation at baseline and the 3 visits. Models were scanned with a CAD/CAM scanner (Planmeca, Helsinki, Finland).Canine retraction was significantly greater (1.60 ± 0.38 mm) on the experimental side compared with the placebo side (0.79 ± 0.35 mm) (P <0.05). Pain was significantly less on the experimental side only on the first day after application of LLLI and at the second visit (1.4 ± 0.82 and 1.4 ± 0.64) compared with the placebo sides (2.2 ± 0.41 and 2.4 ± 1.53).Low-level laser irradiation applied at 3-week intervals can accelerate orthodontic tooth movement and reduce the pain associated with it.Force application during orthodontic tooth movement (OTM) causes pain.Low-level laser therapy (LLLT) accelerates tooth movement and reduces pain.Multiple and frequent applications of low-level laser (LLL) have been attempted in past.We applied LLLT at 3-week intervals and used self-ligating brackets (SLB).LLLT every 3 weeks accelerates OTM and reduces pain when SLB are used.