Diabetic macular edema (DME) is the primary cause of vision loss in people with diabetes, and if untreated, it can result in irreversible macular damage. Both fluorescein angiography (FA), the gold standard, and optical coherence tomography angiography (OCTA) are used for evaluation of this disease. The objective of this study was to compare the diagnostic value of both. We conducted a comparative analysis of 98 patients aged 18-80 years with significant DME and best-corrected visual acuity ≥0.1 according to the Snellen chart. Participants underwent glycated hemoglobin blood test (HbA1c) and ophthalmological examinations, including OCTA and FA. OCTA 3 × 3 mm scans of superficial (SCP) and deep capillary plexus (DCP) along with FA scans were exported to the Gimp computer program. Size of the foveal avascular zone (FAZ), the number of visible microaneurysms (MAs), and ETDRS report number 11 classification of the images were assessed. FAZ size differed significantly in superficial plexus (0.41 mm), deep plexus (0.43 mm) OCTA, and FA (0.38 mm) ( < 0.001). FAZ size in DCP OCTA closely correlated with that of FA (τ = 0.79, < 0.001). The total number of MAs visualized in the OCTA was significantly lower than in FA ( < 0.001). ETDRS classification of scans revealed that the level of consistency between the examinations was moderate to very strong. OCTA may be useful in evaluating macular ischemia. It is less sensitive in detecting MAs in DME eyes. FAZ has sharper boundaries and is larger when measured in OCTA. Poor glycemic control results in higher incidence of MAs in macula.