The purpose of the study is to compare the visual outcome of occlusion versus penalization treatment of strabismic amblyopia, with particular attention to binocularity outcome. The study design was a retrospective study. Patients with strabismic amblyopia, 75 receiving penalization alone, 87 with a history of occlusion treatment who were later treated by penalization, and 30 treated by means of part-time occlusion (2 to 6 hours/day) participated in this study. Logarithm of the minimum angle of resolution (logMAR) visual acuity and binocularity index were measured. No statistically significant difference was found between outcomes for the penalization groups with and without a history of occlusion, either by univariate analysis or by multivariate analysis controlling for initial-visit age, acuity, and binocularity status. One marginally significant outcome difference was found between the pure penalization and part-time occlusion groups by univariate analysis, but no significant difference was found in the multivariate analyses controlling for the same three variables at the initial visit. All visual outcome differences between the pure penalization and part-time occlusion groups were less than 1 logMAR line visual acuity or less than a half-unit on the binocularity index. The study provided no evidence of a difference in visual function outcome between penalization and occlusion, in terms of either statistical or clinical significance, although limitations of the patient samples used preclude these data from showing conclusively that there was no such difference. The lack of any other study adequately comparing these two treatment methods, in combination with the current study's demonstration of the difficulty of making adequate retrospective-based comparison despite a large patient base (n = 1413), suggests that a large prospective, randomized comparative treatment trial is needed. If atropine penalization, with its high acceptability to patients and parents, is found to produce results comparable with those of occlusion in cases of mild-to-moderate amblyopia, as the current and previous smaller studies suggest, then reconsideration of the standard of care for such amblyopia cases is indicated.