Background Semipermeable gloves might be an alternative to cotton gloves in management of hand dermatoses. Objectives To compare acceptance and tolerability of gloves made of cotton or a semipermeable Sympatex membrane in patients with hand dermatoses and their effect on skin lesions when worn overnight. Methods A total of 199 patients with work‐related symmetrical hand dermatoses were asked to wear a cotton glove (COT) on one hand and a Sympatex glove underneath a cotton glove (SYM/COT) on the other hand for 19 consecutive nights. The severity of skin lesions was regularly examined. A questionnaire on acceptance and tolerability was used in a subset of 126 patients. Results Data on skin lesions were available for 183 participating patients (92%). The severity did not differ substantially between hands covered with SYM/COT or COT over time. Questionnaire data were available for 120 patients (95%). SYM/COT received better ratings regarding climate conditions while COT showed superiority in wearing comfort, practicality and appearance. Conclusions Both SYM/COT and COT were well tolerated and accepted in patients with hand dermatoses. Hence, SYM/COT may serve as suitable alternative for COT as comfort gloves supporting therapeutic efforts. The observed slight differences may influence the decision when selecting the glove type. Highlights Wearing of either SYM/COT or COT for several hours overnight is similarly well tolerated and accepted in patients with hand dermatoses. SYM/COT received better ratings regarding climate conditions while COT showed superiority in wearing comfort, practicality and appearance. SYM/COT may serve as an alternative for COT in the application as comfort gloves supporting therapeutic efforts, especially for longer application periods.