This study compares the development of reflux, recanalization, and clinical outcomes of patients with femoral-popliteal and iliofemoral deep venous thrombosis (DVT). Emphasis is placed on the relationship between early lysis of clot through thrombolysis and the development of reflux and post-thrombotic syndrome (PTS) for iliofemoral patients. A retrospective chart review was conducted of 27 femoral-popliteal DVT limbs and 11 iliofemoral DVT limbs with average follow-up of 2.3 and 2.1 years, respectively. Rates of recanalization, development of reflux, and post-thrombotic syndrome were recorded through review of duplex scans and physical examinations. All femoral-popliteal patients received anticoagulant therapy. Nine of 11 iliofemoral patients (82%) received thrombolytic therapy in addition to anticoagulants. Statistical analysis included Kaplan-Meier estimation to take into account dropout in follow-up times, and chi-squared analysis to compare final outcomes. A significantly greater proportion of iliofemoral patients (73%) than femoral patients (31%) remained asymptomatic at the end of their follow-up (p < 0.025). Because of thrombolytic therapy, 82% of iliofemoral limbs showed partial or complete lysis 4 weeks after diagnosis of clot. As expected, only 22% of femoral-popliteal limbs developed some recanalization 4 weeks after diagnosis (p < 0.005). Interestingly, no significant difference in reflux development was observed between the two groups. After an average of 2.1 years, 60% of femoral-popliteal limbs developed reflux in the deep veins vs. 64% for iliofemoral limbs. The iliofemoral DVT patients showed improved clinical outcomes in the short term compared to that of femoral-popliteal patients in this pilot study. The improved clinical outcomes could be attributed to the early lysis of clot via thrombolytic therapy for the iliofemoral group. Although the extent of reflux development was similar in both groups, iliofemoral patients still showed fewer clinical symptoms after follow-up. This may suggest that the presence of both residual obstruction and reflux, rather than either one alone, significantly increases the chances for development of PTS. Since thrombolytics eliminates at least one of these factors, residual obstruction, it may aid in decreasing development of PTS in the short term. The data in this retrospective study warrant further long-term prospective analysis of thrombolysis and its relationship with PTS.