Purpose This study seeks to investigate the use of extra-orally applied near-infrared phototherapy for the reduction of oral pain secondary to chemotherapy- and radiation therapy-induced mucositis in adult and pediatric hematopoietic stem cell transplant (HSCT) patients. Methods Eighty HSCT patients were divided into regular (R) and low (L) risk groups, then to experimental (E) and placebo (P) groups, resulting in four groups (ER, EL, PR, PL). Experimental subjects received 670 (±10) nm gallium-aluminum-arsinide light-emitting diode device for 80 s at ∼50 mW/cm2 energy density and power exposure of 4 J/cm2. Placebo patients received the same procedures, but with a placebo phototherapy (identical device but /cm2 energy density). Patients received their respective light therapy once per day starting on the day of the HSCT (day 0) and continued through day +14. Blinded evaluators examined the patients three times per week and scored their oral tissues and patient-reported pain assessments at each evaluation utilizing the WHO, NCI-CTCAE, and OMAS scales. Results Analysis of the mean scores at each observation demonstrate that the extra-oral application of phototherapy resulted in a significant reduction in patient-reported pain between the ER and PR patients (p  < 0.05) at day +14 when graded via the WHO criteria. The ER and EL patients were improved in almost all other categories and assessment scales, but the differences were not statistically significant. Conclusion Phototherapy demonstrated a significant reduction in patient-reported pain as measured by the WHO criteria in this patient population included in this study. Improvement trends were noted in most other assessment measurements.