Purpose: To compare outcomes of contemporary mechanical thrombectomy for iliofemoral deep vein thrombosis (IF-DVT) vs isolated femoropopliteal DVT (iFP-DVT). Methodology: The CLOUT study (NCT03575364) evaluated mechanical thrombectomy with the ClotTriever system (Inari, Irvine, CA, US) for proximal lower extremity DVT. Here, outcomes were assessed after grouping subjects by anatomical disease location. The primary effectiveness endpoint was ≥75% postprocedural thrombus removal based on independently adjudicated Marder scores. Additional outcomes, including postthrombotic syndrome (PTS) by Villalta score, were collected through 2-year follow-up. Results: After grouping by DVT location, IF-DVT was present in 389 (78.6%) limbs from 379 subjects, and iFP-DVT was present in the remaining 106 (21.4%) limbs from 105 subjects. In the IF-DVT group, there was a larger proportion of female subjects (53.3% vs 41.6%, P=.0436), but no other significant differences in baseline characteristics were observed. A comparable proportion of limbs in each cohort achieved the primary endpoint of ≥75% thrombus removal (90.5% vs 93.4%, P=.4415). Comparing the IF-DVT and iFP-DVT cohorts, treated limbs demonstrated similar improvements in patency from baseline (18.4% vs 11.8%, P=.1924) through 2-year follow-up (94.9% vs 90.0%, P=.2699). There were no significant differences in Villalta score between the IF-DVT and iFP-DVT groups at any study visit, improving from baseline (median score 9.0 vs 10.0, P=.2732) through 2-year follow-up (median score 1.0 vs 2.0, P=.7186). At the 2-year visit, the distribution of PTS severity was not significantly different in the IF-DVT vs iFP-DVT cohorts (none: 80.6% vs 81.4%, mild: 13.6% vs 8.5%, moderate: 3.7% vs 6.8%, severe: 2.1% vs 3.4%; P=.4695). Conclusion: Mechanical thrombectomy achieved similar outcomes in IF-DVT and iFP-DVT. Additional research is warranted to better understand the benefits and limitations of this intervention for patients with iFP-DVT.