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Background Deep venous thrombosis isolated to the iliac veins is uncommon. Venous duplex ultrasound (DU) is widely accepted as the screening modality of choice for lower extremity deep venous thromboses. This investigation evaluated the accuracy and efficacy of DU in diagnosis of iliac vein thrombosis. Methods We conducted a single-center retrospective review of patients who were diagnosed with iliac vein thrombosis between January 1, 2006, and December 31, 2015. Patients included in our analysis needed to have both DU and cross-sectional imaging performed within a month of each other. The efficacy of DU in diagnosis of iliac vein thrombosis was determined using cross-sectional imaging as a standard for diagnosis. Results In total, our query yielded 80 patients with a diagnosis of iliac vein thrombosis in the medical chart; 48 patients had both cross-sectional imaging and DU performed within 1 month of each other. There were 36 patients who had cross-sectional imaging positive for iliac vein thrombosis; only 10 (27.8%) of these patients were found to have iliac vein thrombosis by DU. Thus, 26 patients (72.2%) were not diagnosed accurately by DU. On the basis of our data, the sensitivity and positive predictive value of DU compared with cross-sectional imaging in diagnosis of iliac vein thrombosis were 27.8% and 76.9%, respectively. We did not identify any patient-specific factors that influenced the discrepancy between DU and cross-sectional imaging. Conclusions Our current protocol of lower extremity venous DU is not an effective tool in diagnosis of iliac vein thrombosis. All patients with clinically suspected iliac vein thrombosis should be evaluated with specific pelvic ultrasound protocols or cross-sectional imaging.