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Introduction: Hemiparesis post-stroke usually results in locomotor limitations. As conventional rehabilitation is monotonous, the Serious Games (SG) represents an excellent treatment strategy, allowing to perform physical training in an interesting and enjoyable way. Objective: To evaluate the effects of an exercise program using the SG developed for hemiparetic stroke patients’ locomotor rehabilitation. Method: Non-Randomized Controlled Clinical Trial. Twenty-four hemiparetic stroke patients with subacute or chronic stroke (twelve men), mean age of 57.8 ± 10.4 years (injury time of 16.8 ± 19.6 months) participated in the study. The experimental group (n = 16) participated in an exercise program with the SG for lower limb rehabilitation. The control group (n = 8) received conventional treatment (kinesiotherapy). The intervention consisted of sessions twice a week for ten weeks. The following parameters were assessed: muscle strength (dynamometry), spasticity (Modified Ashworth Scale), functional mobility (Timed Up and Go Test - TUGT), and the gait speed (GS). Results: Both groups showed improvements, but the experimental group was better in all the studied variables, the muscular strength of the lower limb paresis and of the quadriceps femoris (p = 0.002; d = 0.7); and for the hamstrings (p < 0.001; d = 1.3), TUGT (p < 0.001; d = 0.4), and GS (p = 0.001; d = 0.4). Conclusion: The exercise program with the SG was useful for the patients treated in this study. The results showed a superiority of the SG regarding the conventional treatment in all the controlled variables. This was probably because of the greater repeatability of the exercises and the increased attention and motivation.