INTRODUCTION: Scalp cooling is standard-of-care for prevention of chemotherapy-induced alopecia (CIA), with proven safety and efficacy. Limb cryotherapy has shown promise in preventing chemotherapy-induced peripheral neuropathy (CIPN). The safe application of concomitant scalp and limb cryotherapies during chemotherapy is crucial due to concerns about potential interactions, including central hypothermia, yet limited data exist on their safe delivery in this context. Here we report a prospective, single-arm study assessing feasibility, safety, and tolerability of concomitant scalp cooling and limb cryocompression in healthy volunteers, and in cancer patients undergoing chemotherapy. METHODS: Safety and tolerability of concomitant scalp cooling and limb cryocompression were evaluated in healthy volunteers and then in cancer patients receiving weekly paclitaxel chemotherapy. Limb cryocompression was administered starting at 11 °C, with thermoregulation allowed up to 25 °C to accommodate patient tolerance. Core body temperature changes, adverse events (CTCAE v4.0), and tolerance to cryotherapy were documented. EORTC Quality of Life Questionnaire-CIPN20 scores were evaluated before the start of chemotherapy (QoL RESULTS: Concomitant scalp and limb cryocompression at 11 °C was safe and tolerable in healthy volunteers (n = 3). Fifteen patients enrolled in the study and 13 completed the entire treatment, with negligible core body temperature changes (- 0.18 °C ± 0.37). Eight patients completed all 12 cycles of cryocompression at 11 °C while some required thermoregulation (range 14 °C to 18 °C). One patient completed all cryotherapy cycles at 25 °C and another withdrew due to intolerance to 25 °C. There were no occurrences of ≥ Grade 2 neuropathy. QoL was preserved and scores remained stable at QoL CONCLUSION: Delivery of concomitant scalp cooling and limb cryocompression is feasible, safe, and tolerable. Larger studies are needed, and currently ongoing, to investigate the efficacy of limb cryocompression for CIPN prevention.