Background: Chemotherapy induced alopecia (CIA) significantly impairs QoL. Scalp cooling devices typically used at -5°C decrease CIA. However, there is still room to improve efficacy with anthracycline therapy. This prospective study was performed to evaluate the safety, tolerability, and efficacy of the Paxman Scalp Cooling System (PSCS)® when used at cooler temperatures of -7.5°C and -10°C. Methods: Patients with stage I-III breast cancer receiving anthracycline chemotherapy at Memorial Sloan Kettering Cancer Center from 12/23/2019 – 10/12/2022 were enrolled on this IRB-approved study. They were evaluated for hair loss at baseline, weeks 4, 8 (primary endpoint), end of treatment, and 24 weeks post treatment using clinical photography and trichoscopy, which measures hair width and count. Degree of hair loss was graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4. Successful hair preservation is indicated by alopecia grades 0 and 1. Results: 34 patients (mean age 44) used the PSCS at cooler temperatures with no DLTs. 7 patients received scalp cooling at -7.5°C and 27 patients at -10°C. 19 women (55.9%) were included in the final analysis; 7 patients withdrew or were taken off study prior to the primary endpoint and 8 patients did not successfully complete photographic or trichoscopic follow-up assessments. At the baseline visit, 95% of patients had grade 0 alopecia (n = 18) and 5.3% had grade 1 alopecia (n = 1). At week 8 (primary endpoint) 53% of patients had grade 1 alopecia and 47% had grade 2 alopecia. At completion of therapy, 7% of patients had grade 0 alopecia, 36% had grade 1 alopecia, 7% are pending and 50% had grade 2 alopecia. At 24 weeks post treatment completion, 23% of patients had grade 0 alopecia (n = 3), 31% had grade 1 alopecia (n = 4), and 46% of patients are pending results (n = 6). At baseline, the average hair count was 149.0 per cm² (n = 19) and the average hair width was 68.9μm (n = 19). At week 4 and 8, there was a -27% and -8.9% change in hair count and -8.6% and -9.3 percent change in hair width (n = 18) respectively. By end of treatment, percent change was -37.8 and -11.6 for hair count and hair width, respectively (n = 14). At 24 weeks post treatment completion, both the average hair count and hair width for patients were higher compared to their baseline (hair count = 242 per cm² and hair width = 70.7μm (n = 13; 6 patients pending). Conclusions: Overall, use of the PSCS for successful hair preservation is effective, safe, and tolerable at lower temperatures for patients being treated with anthracycline chemotherapy. 43% of patients had hair preservation at the completion of the study. At 24 weeks post treatment, the average hair count and width was higher than the values at baseline indicating thicker, full hair regrowth. None of the patients displayed grade 2 alopecia at 24 weeks post treatment, allowing patients to avoid the use of a wig to hide resulting CIA. Clinical trial information: NCT04180579.