Background and Objectives: To determine the efficacy, durability, and safety of a single treatment with intravitreal ranibizumab plus peripheral scatter laser (RaScaL) in patients with diabetic macular edema associated with peripheral retinal nonperfusion on ultrawide-field fluorescein angiography (UWFA). Study Design: A 6-month, randomized, controlled, prospective phase I/II study of 30 treatment-naïve eyes of 22 patients (8 bilateral patients) with visual impairment secondary to diabetic macular edema associated with peripheral nonperfusion on UWFA. Patients were randomized to receive ranibizumab plus UWFA-guided peripheral scatter laser (n = 15) or triamcinolone acetonide plus macular laser (n = 15). Results: At 6 months, the RaScaL group patients had fewer recurrences warranting retreatment (33% vs. 80%, p < 0.003). Mean change in final visual acuity and central foveal thickness were not statistically significant between groups. Conclusion: This pilot study suggests the efficacy, safety and durability of the RaScaL treatment regimen in patients with diabetic macular edema associated with peripheral nonperfusion on UWFA.