Background: Various socket designs exist, linking the residual limb together with the prosthetic components to restore the ability to walk; however, lack of socket comfort is a frequent complaint. Objective: To evaluate the impact of socket design on end-user comfort and mobility. Methods: A randomized crossover trial was set to compare comfort and mobility of above-knee amputees (AKAs) wearing an ischial containment (IC) or subischial (I-SUB) socket. Patients actively wearing IC sockets were recruited from 10 rehabilitation centers across the country. They were then fitted for an I-SUB socket by Certified Prosthetists (CPs) as an alternate socket. Participants were randomly assigned to start with one or the other socket. After a minimum of 2 weeks, each participant evaluated the Socket Comfort Score (SCS) (primary outcome) in various situations, performed the 2-min walk test, and answered the PLUS-M questionnaire (secondary outcomes). Results: A total of 25 participants were included, of whom 23 completed the study with full (n = 21) or partial data (n = 2). SCS were improved with I-SUB compared with IC in all situations, with significant differences in general, when sitting on a rigid chair, sitting in a car, and standing. The differences in self-reported mobility and walking distance at the 2-min walk test were not significant. At the end of the study, more than 80% of the participants chose to keep the I-SUB socket for their daily use. Conclusions: For the first time, this study supports that the subischial suction socket improves comfort in daily life without negatively impacting user mobility in a group of individuals with AKA.