To compare the effects of an upper limb videogame-based training with a training based on similar motor demands on upper limb function, dexterity, functionality, balance, fatigue, and pain in post-polio syndrome (PPS) and to assess the acceptability, feasibility, and safety of the intervention. This is a randomized, parallel, single-blind clinical trial. Thirty-nine individuals were randomized into Interactive Videogames Group (IVG, = 19) and Active Exercises Group (AEG, = 20). Participants performed two weekly sessions (50 minutes each), totaling 14 sessions with the aim of providing mild to moderate intensity. IVG practiced four Nintendo Wii Sport games (tennis, golf, boxing, and bowling). The AEG performed similar movements required for IVG. Primary outcome: upper limb motor function-Motor Function Measure-32. Secondary outcomes: dexterity-Box and Block test; functionality-Functional Independence Measure; balance-Functional Reach Test, muscle fatigue-Fatigue Severity Scale, upper limb pain-Visual Analogue Scale for pain, acceptability, applicability, and safety. Analysis of group, time, interaction between groups, and time effects was performed through repeated-measures analysis of variance (2 × 3) and Bonferroni post hoc test with alpha of 0.05. Interactive videogames were safe, feasible, and acceptable. Both groups showed similar postintervention improvement on motor function, functionality, balance, pain, and fatigue, with maintenance over the follow-up period. There was an interaction effect between the groups on dexterity and the IVG demonstrated better performance compared with the AEG. The similar positive clinical effects of the interactive video games on PPS upper limb function and its superior effects on dexterity support its use as a safe and feasible intervention. Particularly when it comes to chronic patients, who require long-term physical therapy, new and stimulating interventions may contribute to the rehabilitation process and improve their engagement in the treatment. Registered on the Brazilian Clinical Trials platform under number RBR-8S2NBF.