Despite being becoming popular and heavily used in rehabilitation, the evidence on the effectiveness of Virtual reality-based therapy (VRBT) among persons with knee osteoarthritis (OA) remains limited. The aim of this study was to determine the effects of VRBT on walking endurance and quality of life of older persons with knee OA in comparison to conventional exercise therapy. This was a randomised controlled trial involving 44 participants (mean age and standard deviation = 66.32 ± 5.73 years) who received either a VRBT (experimental group, n = 22) or a conventional exercise therapy (control group, n = 22) for 45 minutes, twice per week for 12 weeks. The outcome of both therapies on walking endurance was measured using Six-Minute Walk Test (6 MWT), while quality of life was assessed using the Malay-version of Short Form-36 (SF-36). Analysis was done by ‘intention-to-treat’ approach, using Mixed Model ANOVA. A significant time-effect (p < 0.05), with large effect size between 0.43 and 0.54 were found for all outcomes following the therapies. An increase of 17% and 19% of 6 MWT scores were obtained in experimental and control group, respectively. Meanwhile, the scores for the physical and mental components of the SF-36 increased by 37.8% and 19.4% in the experimental group, and 45.7% and 20.6% in the control group. However, no significant group and interaction effects were found for all outcomes (p > 0.05). In conclusion, VRBT is comparable with conventional exercise therapy in improving walking endurance and quality of life of persons with knee OA, and can be used as a therapy option for this population.