Objective: To investigate the effects of gender and gloves on hand fatigue, measured by the reduction in grip strength (ΔMVC), the shift in time needed to reach maximal voluntary contraction (MVC; ΔTMVC), and the maximal endurance time (MET). Background: Information about the effect of gloves on muscle fatigue seems to be less plentiful than that on hand strength, dexterity, sensation, and so on. Method: Ten male and 10 female volunteers served as participants. A task of sustained gripping until exhaustion was used as the designated fatigue protocol. Three gloved conditions were evaluated: bare-handed and single (Cotton 1) and double (Cotton 2) cotton gloves. Results: After completion of the fatigue protocol, a greater reduction in grip strength was found for men than for women in both magnitude and percentage. Male ΔTMVC was significantly greater; that is, there was more delay in time needed to reach the MVC for men than for women when the fatigue protocol was completed. MET was longer for men than for women. During gloved conditions, except for the ΔMVC, glove use did not change any of the other responses. Specifically, the gloved effect on ΔMVC depended upon gender. Conclusion: Men had a greater reduction in grip strength and took longer to reach the MVC than did women after the fatigue protocol. Except for decreasing the ΔMVC, whether or not gloves were worn did not change any of the other responses. Application: These data are useful for glove design, manufacture, and selection.