Purpose Frozen gloves (FG) are effective in preventing docetaxel-induced nail toxicity (DNT), but uncomfortable. The preventive effect of FG for DNT was compared using a standard (−25 to −30°C) or more comfortable (−10 to −20°C) preparation. Methods Breast cancer patients receiving docetaxel were eligible. Each patient wore an FG (prepared at −10 to −20°C for 90 min) for 60 min without replacement on the right hand. The left hand was protected by standard methods (FG prepared at −25 to −30°C overnight and worn for 90 min with replacement at 45 min). The primary endpoint was DNT occurrence at 5 months. Secondary endpoints included docetaxel exposure [cumulative dose and area under the blood concentration time curve (AUC)] until DNT occurrence and discomfort from FG. The pharmacokinetics of docetaxel was assessed. Results From 23 patients enrolled between December 2006 and June 2010, seven who received docetaxel for less than 5 months were excluded from evaluation. The median accumulated docetaxel dose was 700 mg/m2 (340–1430 mg/m2). Within 5 months of FG use, none developed protocol-defined DNT in either hand. Two patients (13%) developed DNT at 7.2 and 7.3 months, respectively, both at −10 to −20°C. In the control hand (−25 to −30°C), discomfort occurred in 92% of the cycles, compared to 15% in the experimental hand (−10 to −20°C). Five patients (22%) experienced pain at −25 to −30°C, but none did at −10 to −20°C. The degree of docetaxel exposure was not related to DNT occurrence in our study. Conclusion A convenient preparation of FG at −10 to −20°C is almost as effective as a standard preparation at −25 to −30°C, with significantly less discomfort.