Endovascular management of complex aortoiliac occlusive disease (AIOD) has been described as a viable alternative to open surgical reconstruction. To date, few studies have directly compared the two techniques. We therefore, evaluated short- and midterm outcomes of open and endovascular therapy in TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) D AIOD patients. TASC II D patients undergoing treatment between January 2009 and Dec 2016 were retrospectively reviewed. Patient demographics, clinical data, and outcomes (technical and systemic complications and graft patency) were collected. The primary outcome of this study was primary graft patency. Patients were compared according to treatment group (open vs endo). Kaplan-Meier curves were used to analyze follow-up results. The analysis included 75 patients (open: 30; endo: 45). In the endovascular group, 27 patients (60.0% of endo) were managed using a hybrid approach with 100% technical success. Critical limb ischemia was the indication for intervention in 37.3% of this cohort (open, 40.0% vs endo, 35.6%; P = .397). Overall, there were no significant differences in gender (male: open, 50.0% vs endo, 55.6%; P = .646) or age (open, 54.5 ± 6.0 years vs endo, 56.9 ± 8.7 years; P = .280). No in-hospital deaths occurred in this cohort. The overall complication rate was significantly higher in the open group (open, 43.3% vs endo, 17.8%; odds ratio [OR], 3.5; 95% confidence interval [CI], 1.2-10.1; P = .016) with perioperative systemic complications being more likely in the open cohort (open, 40.0% vs endo, 6.7%; OR, 9.4; 95% CI, 2.3-37.1; P < .001), while technical complications did not differ between the two groups (open, 6.7% vs endo, 11.1%; OR, 0.6; 95% CI, 0.1-3.1; P = .695). Follow-up data were available for 68 patients (90.7%), for a mean of 21.3 ± 17.1 months. Reintervention rates were significantly higher in the endo group (open, 3.3% vs endo, 20.0%; OR, 7.2; 95% CI, 1.1-14.3; P = .038). The overall primary patency was significantly higher in the open group (open, 96.7% vs endo, 80.0%; OR, 7.3; 95% CI, 1.1-60.5; P = .038). Kaplan-Meier curves revealed separation of the primary outcome for open therapy relative to endovascular repair (log-rank, P = .320; Fig). In this head-to-head comparison of open and endovascular therapy for complex AIOD, endovascular therapy was associated with high initial technical success and fewer in-hospital systemic complications but also high reintervention rates when compared to open repair. Further prospective studies aimed at reduction of complications, optimization of patency, and patient selection for such procedures is warranted.