BACKGROUND: The efficacy of treating anisometropic amblyopia with occlusion therapy is well known. However, this form of treatment can be associated with risks. Spectacle correction alone may be a successful and underutilized form of treatment. METHODS: The records of 28 patients treated successfully for anisometropic amblyopia with glasses alone were reviewed. Age, initial visual acuity and stereoacuity, and nature of anisometropia were analyzed to assess associations with time required for resolution, final visual acuity, and stereoacuity. Incidence of amblyopia recurrence and results of subsequent treatment, including patching, were also studied. RESULTS: Mean time to amblyopia resolution (interocular acuity difference <or=1 line) was 5.8 months (range 2 to 15 months). Worse best corrected initial visual acuity was associated with longer time to resolution (Spearman’s rho = 0.37, P = 0.05), while age, initial stereoacuity, amount, and type of anisometropia were not (P = 0.43, 0.68, 0.26, 0.47, respectively). None of the astigmatic or myopic patients achieved visual acuity of 20/20 in the amblyopic eye, while seven (39%) of the hyperopic patients did. This difference was significant (P = 0.03). Better initial stereoacuity predicted good final stereoacuity (P = 0.01). Only four (14%) patients developed amblyopia recurrence over an average follow-up period of 1.7 years. All were successfully treated with updated spectacles or patching. CONCLUSIONS: Treatment of anisometropic amblyopia with spectacles alone can be a successful option. Patients treated with spectacles alone may experience a lower amblyopia recurrence rate than those treated with occlusion therapy.