The effect of low-level laser therapy with high photon energy wavelengths, green and violet, for treating chronic musculoskeletal pain was examined in the first-ever clinical trial of its kind. Participants (n = 43) underwent a single 13-minute laser session. The primary measure of effectiveness was the change in initial visual analog pain (VAS) scores observed three minutes posttreatment. The success of a participant was defined in advance as a reduction of ≥30% in VAS scores, while the success of the study was predetermined as achieving a 65 ± 5% success rate among individual participants. Results demonstrated subjects’ VAS pain scores decreased from 71.79 to 34.02 (p < 0.0001), while most participants in the study (81.4%) achieved a ≥30% decrease in pain scores. The findings from this clinical investigation provided substantial support for the first Food and Drug Administration clearance (K221987) for the combined application of green and violet lasers.