To evaluate the effects of an exergame-based intervention on a population sample of women with fibromyalgia. Single-blinded, randomized controlled trial with 8-week intervention. Fibromyalgia center. Participants (all women) (N=83) were divided into 2 groups: an exercise group (n=42; mean age ± SD, 52.52±9.73y) and a nonexercise group (n=41; mean age ± SD, 52.47±8.75y). Women in the exercise group completed an 8-week exergame-based training program, which was focused on postural control and coordination of the upper and lower limbs, aerobic conditioning, strength, and mobility. Women (groups of 3) were encouraged to exercise for 120 minutes (over 2 sessions) per week. Main outcome measures included pain and disease effect, which were assessed with the Fibromyalgia Impact Questionnaire (FIQ), a specific measure for fibromyalgia. Secondary outcome measure included quality of life, which was assessed with the EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) generic instrument. The results showed that 97.62% of participants in the exercise group completed the 8-week intervention. The exercise group showed a significant improvement (P<.05) in the EQ-5D-5L utility index, and in 3 of 5 dimensions. For the FIQ, significant improvements were observed in the dimensions of pain, stiffness, anxiety, and feel good. The FIQ score was also reduced. The mean between-group improvement was 8.25 (95% confidence interval, 2.85-13.65). The results and levels of compliance/adherence suggest this exergame-based training program is an effective intervention for reducing pain and increasing health-related quality of life in women with fibromyalgia.