Abstract.[Purpose] The purpose in the present study was to examine the possibility that virtual reality interactive exercise game can help relieve depression and improve the quality of life of elderly females with osteoarthritis.[Subjects and Methods] Forty elderly females suffering from knee osteoarthritis were randomly assigned to either an experimental group or a control group so that each group had 20 members. The experimental group played exercise game using Xbox 360 kinetic sensors for 30 minutes per session, three times a week for four weeks. The control group did not engage in this activity. The depression of the subjects was measured using the Korean version of the Short Geriatric Depression Scale (SGDS-K) and their quality of life was measured using SF-8.[Results] The experimental group's SGDS-K score after the exercise game intervention was significantly lower than that before the intervention and the experimental group's SGDS-K score was significantly lower than that of the control group. The experimental group's SF-8 score after the intervention was significantly higher than that before the intervention and the experimental group's score was higher than that of the control group, although the differences were not significant.[Conclusion] The exercise game experiment using Xbox 360 kinetic sensors showed the possibility that such activities could help relieve depression and improve the quality of life of elderly females suffering from osteoarthritis. Further studies are necessary to determine the most effective methods and duration.