AIM: To compare two different anti-vascular endothelial growth factor (anti-VEGF) treatment regimens’-a priori pro re nata (PRN) and PRN regimen following the loading phase-anatomical and functional results in neovascular age-related macular degeneration (nAMD) patients. METHODS: Totally 544 nAMD patients followed and treated with aflibercept (n=135) and ranibizumab (n=409) at 9 different centers between 2013 and 2015 were enrolled into this retrospective multicenter study. Patients with initial best corrected visual acuity (BCVA) interval of 1.3-0.3 (logMAR) and a minimum follow-up of 12mo were included. Patients under two different regimens-a priori pro re nata (1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen (3+PRN)-were compared in BCVA at 3th, 6th and 12th months, and in central macular thickness (CMT) at 6th and 12th months. The total study group, intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in the 1+PRN (n=101) regimen from 407 to 358 and 340 μm and in the 3+PRN (n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically, the CMT reduction at 6th month (48.5 vs 76.4; P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75; in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3th month (-0.01 vs 0.12; P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6th (44 vs 72) and 12th month (61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3th month (-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction (61 vs 89, 6th month; 85 vs 97, 12th month) and visual gain (0.02 vs 0.16; 0.02 vs 0.14; 0.05 vs 0.11) was found in favor of 3+PRN group at all visits. CONCLUSION: The loading dose of anti-VEGF treatments in nAMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.