To identify factors that predict the success or failure of treatment with intravitreal ranibizumab for patients with diabetic macular edema. A total of 37 baseline demographic, systemic, ocular, optical coherence tomographic, and fundus photographic variables were assessed for association with change in visual acuity or central subfield thickness between baseline and 1 year in 361 eyes that were randomly assigned to intravitreal ranibizumab with prompt or deferred laser treatment within a trial of ranibizumab, triamcinolone acetonide, and laser treatment for center-involved diabetic macular edema. A categorical variable describing follow-up anatomic responses to therapy was added to the visual acuity outcome model. After adjusting for baseline visual acuity, a larger visual acuity treatment benefit was associated with younger age (P< .001), less severe diabetic retinopathy on clinical examination (P= .003), and absence of surface wrinkling retinopathy (P< .001). The reduction in central subfield thickness during the first treatment year also predicted better visual acuity outcomes (P< .001). After adjusting for baseline central subfield thickness, the presence of hard exudates was associated with more favorable improvement on optical coherence tomographic scan (P= .004). Because only 11 eyes experienced vision loss and 6 eyes experienced an increase in central subfield thickness, factors for poor outcomes could not be evaluated. A review of baseline factors and anatomic responses during the first year of ranibizumab therapy for association with visual acuity outcome did not identify any features that would preclude ranibizumab treatment. However, baseline central subfield thickness is the strongest predictor of anatomic outcome, and reduction in central subfield thickness during the first treatment year is associated with better visual acuity outcomes.