OBJECTIVE To compare a smartphone-based dichoptic video game with occlusion therapy in children with anisometropic amblyopia. METHODS In this prospective, randomized, interventional study, 55 children aged 5 to 15 years with anisometropic amblyopia were randomized into two groups: the video game group (n = 27) played a dichoptic video game with adjusted contrast for 2 hours/day and the patching group (n = 28) received occlusion therapy of the non-amblyopic eye for 6 hours/day. All patients were evaluated for best corrected visual acuity (BCVA), near vision, contrast sensitivity, and near and distance stereoacuity at baseline and 1, 2, and 3 months. RESULTS Mean distance BCVA improved from 0.74 ± 0.19 and 0.70 ± 0.18 logarithm of the minimum angle of resolution (logMAR) in the video game and patching groups, respectively, at baseline to 0.53 ± 0.19 and 0.49 ± 0.19 logMAR, respectively, at 3 months (P < .001 for both). Mean near vision was 0.82 ± 0.19 and 0.81 ± 0.17 logMAR in the video game and patching groups, respectively, at baseline and improved to 0.60 ± 0.16 and 0.63 ± 0.17 logMAR at 3 months (P < .001 for both). There was no significant difference in distance and near vision between the two groups at baseline and final follow-up visit. Contrast sensitivity was 1.41 ± 0.20 and 1.38 ± 0.20 in the video game and patching groups, respectively, at baseline and 1.74 ± 0.18 and 1.61 ± 0.21 at 3 months (P < .001 for both). At the final follow-up visit, contrast sensitivity was significantly better in the video game group compared to the patching group (P = .01). Near stereoacuity significantly improved only in the video game group (P = .006), whereas distance stereoacuity did not improve in either group. CONCLUSIONS Dichoptic video game therapy showed better results in terms of improvement in contrast sensitivity and near stereoacuity and similar outcomes for distance and near vision when compared to patching in children with anisometropic amblyopia. However, the availability of interesting games is essential to maintain children's interest. [.