Purpose: To identify factors that affect the therapeutic response of intravitreal bevacizumab in diabetic macular edema (DMO) and explore the correlation between the functional and anatomical outcomes observed. Methods: A retrospective, noncomparative, consecutive case series design was used. Baseline imaging data and clinical records of 65 eyes with DMO, secondary to type II diabetes mellitus, which received intravitreal bevacizumab for the first time in 2016, were analyzed. The central macular thickness (CMT), macular volume, and best-corrected visual acuity (BCVA), following the initial 3 injection loading phase were recorded. Outcomes were compared to multiple variables including glycemic control, diabetic retinopathy grade, DMO subtype on optical coherence tomography, and use of past macular laser therapy. Results: The participants' age ranged from 46 to 84 of which 63% were men and 37% were women. The mean baseline CMT was 443.21 μm. A mean reduction of 11.23% (P < 0.0005) in CMT was observed following the loading phase. Women exhibited a greater reduction in CMT (P = 0.032). Participants with diffuse retinal thickening (DRT) and with cystoid macular edema (CMO) showed a net reduction in CMT of 17.39% (P = 0.047) and 8.24% (P = 0.04) respectively. Eyes with proliferative diabetic retinopathy demonstrated a mean gain in CMT of 16.86% (P = 0.001). Conclusions: Female patients and DRT demonstrated a positive anatomical response. Patients with CMO and proliferative diabetic retinopathy displayed a negative therapeutic response. Such observations may be considered in clinical decision-making when opting for anti-vascular endothelial growth factor (VEGF) therapy for DMO.