Purpose <p>Chemotherapy-induced alopecia (CIA) is a prominent side effect of chemotherapy, negatively impacting the patient’s body image and self-confidence. Scalp cooling (SC) has emerged as a preventive option for CIA, but the success rate and adherence vary. Research shows that photobiomodulation (PBM) can improve hair growth by stimulating cell proliferation and repair processes. This trial aims to evaluate the effectiveness of PBM combined with SC in preventing CIA.</p> Methods <p>A randomized, controlled trial with 29 breast cancer patients undergoing taxane-based chemotherapy was performed at the Jessa Hospital (Belgium). Patients were randomized into the control (<i>n</i> = 16) or the intervention group (<i>n</i> = 13). Blinded researchers evaluated scalp coverage and hair thickness, while questionnaires were administered to assess scalp coverage, satisfaction, and health-related quality of life (HRQL). The trial was registered at clinicaltrials.gov (NCT05177289, 4th of January 2022).</p> Results <p>The scalp coverage and hair thickness did not differ significantly between the two groups. Patients in the PBM group scored higher on global health (<i>P</i> = 0.043), physical functioning (<i>P</i> = 0.039), role functioning (<i>P</i> = 0.049), and social functioning (<i>P</i> = 0.038). Patients receiving a paclitaxel-based chemotherapy showed less hair loss compared to patients undergoing a docetaxel-based regimen (Ps &lt; 0.001). No differences in SC adherence could be observed between the two groups.</p> Conclusions <p>The addition of PBM to SC did not increase its efficacy in preventing hair loss during chemotherapy. Patients in the PBM group did score their HRQL higher compared to the control group. Further research is required to establish the use of PBM in CIA prevention and to corroborate these findings.</p>