AIM: To compare three initial monthly intravitreal ranibizumab (IVR) injections followed by pro re nata (PRN) dosing with one initial monthly IVR injections followed by PRN dosing for macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Forty-two eyes of 42 patients who had IVR injections for BRVO were retrospectively studied. Eighteen eyes received 1 initial IVR injection (1+PRN group) and 24 eyes received 3 monthly IVR injections (3+PRN). At 1, 3, 6 and 12mo; spectral-domain optical coherence tomography (SD-OCT) was performed. Central macular thickness (CMT), the integrity of the external limiting membrane (ELM), the presence of subretinal fluid, cyst size, the presence of inner segment/outer segment (IS/OS) defect were determined. RESULTS: At baseline the mean CMT was 521.3±153.2 µm in the 3+PRN group while it was 438.1±162.4 µm in 1+PRN group. At the final visit, mean CMT was 278.3±87.8 µm in the 3+PRN group and 285.2±74.2 µm in the 1+PRN group (P=0.079). The changes in CMT over the entire study period were also comparable in both groups (243±160 µm in the 3+PRN group, and 152.9±175.3 µm in the 1+PRN group; P=0.090). At baseline, best-corrected visual acuity (BCVA) was 0.92±0.60 logarithm of the minimal angle of resolution (logMAR) in the 3+PRN group, while it was 0.72±0.46 logMAR in the 1+PRN group. Final BCVA was 0.42±0.55 logMAR in the 3+PRN group and 0.38±0.50 logMAR in the 1+PRN group (P=0.979). Additionally, the BCVA changes from baseline to final visit were not significantly different (-0.50±0.45 logMAR in the 3+PRN group, and -0.33±0.39 logMAR in the 1+PRN group; P=0.255). CONCLUSION: No significant differences in the anatomical or functional results are found between 3+PRN and 1+PRN regimens in the patients receiving ranibizumab for ME secondary to BRVO. Intact IS/OS and baseline BCVA are good predictor of the visual gain, while baseline CMT is a good predictor of the anatomical gain.