Purpose: To compare the effectiveness of antivascular endothelial growth factor (VEGF) therapy with or without panretinal photocoagulation (PRP) on retinal neovascularization (NV) in patients with proliferative diabetic retinopathy (PDR) at 24 months. Methods: This retrospective, multicenter, observational case series included 237 patients (307 eyes) with retinal NV secondary to PDR treated with anti-VEGF. Results: Eyes were divided into 2 groups: eyes with prior PRP (group A, 162 eyes) and treatment-naïve eyes (group B, 145 eyes). Group A received a mean of 4.5 anti-VEGF injections per eye (95% CI, 4.1-5.1), and group B a mean of 5.8 (95% CI, 5.3-6.3) during follow-up. Both groups showed significant improvements in best-corrected visual acuity and central macular thickness. Mean visual acuity in group A improved from 20/125 to 20/60 (P < .001), and in group B from 20/100 to 20/60 (P = .002). Mean central macular thickness decreased in group A from 341.8 µm (95% CI, 327.2-358.1) to 285.3 µm (95% CI, 273.2-296.4; P < .001), and in group B from 346.1 µm (95% CI, 322.6-365.5) to 298.1 µm (95% CI, 276.2-319.1; P < .001). In group A, 127 eyes (78.4%) responded to anti-VEGF alone. In group B, only 23 eyes (15.8%) achieved complete or partial regression with anti-VEGF alone, while 122 (84.1%) required additional PRP or vitrectomy. Pars plana vitrectomy was performed in 6.7% of group A eyes and 12.4% of group B eyes. Main indications were vitreous hemorrhage and tractional retinal detachment in both groups. Conclusions: Antiangiogenic therapy resulted in marked regression of retinal NV in patients with PDR and previous PRP. A combined approach of antiangiogenics plus PRP should be studied.