This prospective study examined 58 eyes with branch retinal vein occlusion (BRVO) to investigate the effects of the nonperfusion area (NPA), clinical subtype, and crossing pattern on the 2-year outcomes of ranibizumab therapy for the macular edema (ME). All eyes received three initial monthly injections, followed by additional pro re nata (PRN) injections. The final best corrected visual acuity (BCVA) and ranibizumab injection number were not associated with the macular NPA or total NPA at baseline or month 12, and they showed no significant differences between the clinical subtypes. However, the incidence of neovascular changes was higher in the major BRVO group than in the macular BRVO group (P = 0.030). Twelve and 19 of the 34 eyes with major BRVO exhibited arterial overcrossing and venous overcrossing, respectively. At baseline, the total NPA did not differ according to the crossing pattern, however, the total NPA was significantly larger in the venous overcrossing group at month 12 (P = 0.047). At month 24, the incidence of neovascular changes was higher in the venous overcrossing group (P = 0.030). Following ranibizumab therapy for BRVO-associated ME, the clinical subtype and the arteriovenous crossing pattern may be associated with neovascular changes.