Purpose The aim was to compare the effectiveness of catheter directed thrombolysis (CDT) and pharmacomechanical catheter-directed thrombolysis (PCDT) in the treatment of acute, massive iliofemoral deep vein thrombosis. Patients and methods A prospective study was conducted on 50 patients in Zagazig University Hospitals between March 2014 and April 2018. The patients were randomized into two groups. Group A underwent CDT and group B underwent PCDT (ASPIREX). Primary end points were venous patency, complication rate, patient satisfaction, and quality of life Chronic Venous Insufficiency Questionnaire-20. Secondary end points were recurrence and occurrence of post-thrombotic syndrome (PTS), (the Villalta score and revised Venous Clinical Severity Score) within 24 months. Results Aspirex was successful in the majority of patients and grade III, II, and I thrombolysis was achieved in 56, 32, and 12% of patients, respectively, while in the CDT group of patients achieved 44, 36, and 20%, respectively. Recanalization was achieved in 88% patients. At 24 months 32% patients who received CDT presented with PTS compared with 20.83% in the PCDT group after exclusion of one patient who died. Three cases of severe PTS were reported in the CDT group. There was statistically significant difference in PTS at 6 months between the two groups. When comparing Chronic Venous Insufficiency Questionnaire-20 scores between the two groups, there was statistically significant difference between them at 6, 12, and 24 months with more improvement in Aspirex group. Conclusion Aspirex is an effective treatment for lower limb deep vein thrombosis, and the clinical results achieved were superior in comparison with CDT alone.