Purpose: To compare the visual outcome of occlusion therapy with virtual reality game playing as a new therapy for children with amblyopia. Methods: This randomized clinical trial was performed on 50 children between 4 and 10 years old who had unilateral amblyopia. They were randomly divided into virtual reality and patching groups (n = 25 in each). The virtual reality group was trained binocularly using the virtual reality games through a head set for 1 hour per day 5 days a week for 4 weeks. Patients in the patching group occluded their non-amblyopic eyes 2, 4, and 6 hours for mild (best corrected visual acuity [BCVA] 0.2 to 0.3 logarithm of the minimum angle of resolution [logMAR]), moderate (0.3 to 0.6 logMAR), and severe (worse than 0.6 logMAR) amblyopia, respectively. Results: The mean BCVA based on logMAR units improved significantly in both groups ( P < .0001), but the difference between the two groups was not significant ( P = .59). BCVA based on the responded letters improved in both groups (virtual reality: P = .0001, patching: P = .001), and change in BCVA in the virtual reality group was higher than in the patching group ( P = .002). Conclusions: Virtual reality game playing was equal or superior to patching in an analysis of linear and letter BCVA, respectively. Therefore, applying this new amblyopia therapy is recommended. [ J Pediatr Ophthalmol Strabismus . 2021;58(3):154–160.]