Background: Chemotherapy (CT) is a frequent and well established treatment in women with breast and gynecological tumors. Alopecia is one of the most common side effects of CT seriously impairing patient quality of life and body image. While other CT associated side effects can be controlled by supportive treatment strategy, adequate preventive measures for alopecia have been lacking. New evidence supports the efficacy of scalp cooling for alopecia prevention during CT. The aim of this study was to investigate preventive scalp cooling (SC) for chemotherapy-induced-alopecia in breast cancer patients undergoing standard adjuvant or palliative chemotherapy. We also analysed the impact of SC on hair regrowth after chemotherapy-induced-alopecia. Methods: This was a non-randomized, 2-arm interventional study conducted at the Department of Obstetrics and Gynecology, Medical University Innsbruck. Breast cancer patients receiving any chemotherapy associated with alopecia (i.e. taxane or anthracycline-based chemotherapy) were allocated either to an intervention group receiving SC or to a control group (no SC). SC during chemotherapy was applied by the Paxman scalp cooling system. The primary endpoint was hair preservation (HP) which was assessed by experts and patients using the CTCAE score and analysed during and after completion of chemotherapy. The secondary endpoint was hair regrowth (HR) after 3 and 6 to 9 months post chemotherapy. Results: The study population included 128 patients. The majority, namely 88 (69%) patients were assigned to the intervention group (CAP) and received SC, 40 patients were allocated to the control group (NCAP). HP was significantly higher in the group receiving SC than in the NCAP by patients’ self-evaluation (24% vs. 0%; P = 0.001) and experts’ assessment (72% vs. 0%, P ≤ 0.001). HR was comparable between both groups. Using the patients’ evaluation 50% of patients with taxane monotherapy had a grade 1 alopecia compared to 17% of patients with an anthracycline-taxane CT (50% vs 17%, P = 0.018). Drop-out rate was 13% in CAP and 5% in NCAP group. Main reasons for drop-out were hair loss and patients’ requests. Conclusions: Our study demonstrates that SCsignificantly reduced or avoided chemotherapy-induced-alopecia in breast cancer patients undergoing chemotherapy, especially in patients who received taxane-monotherapy. SC was a safe procedure without severe adverse events. Therefore, SC can be highly beneficial for patients receiving specific chemotherapy and the option should be made available to as many patients as possible. No significant effect was noted regarding regrowth after chemotherapy in the SC group.