Background: Acute deep vein thrombosis (DVT) of the lower limbs occurs in about 1.0 person per 1000 population per year and is associated with substantial morbidity. Although anticoagulation effectively prevents thrombus extension, pulmonary embolism, death, and recurrence may occur. Moreover, many patients develop venous dysfunction resulting in post-thrombotic syndrome (PTS). PTS is associated with reduced individual health-related quality of life and a substantially increased economic burden. Hence, additional and more aggressive treatment, including systemic thrombolysis, thrombectomy, and catheter-directed thrombolysis (CDT), has been introduced to accelerate thrombus removal. Numerous studies suggest that additional CDT may provide highly effective clot lysis. There is little doubt that the overall benefit of thrombolysis depends on multiple factors, including predisposing risks, symptom duration, thrombus extension, and technical approaches and interventional success. Aim of the Work: This study aimed to define predictors of immediate and mid-long-term anatomic and clinical failures to guide patient selection and to set a standard for patient and physician expectations. Patients and Methods: This is a prospective observational cohort study that enrolled 20 patients (22 limbs) who presented to the Ain Shams University hospitals in the period from 7/2015 to 7/2017 with acute iliofemoral deep venous thrombosis (IFDVT) and fulfilled the inclusion criteria (mentioned below). Intrathrombus catheter directed thrombolysis (CDT) was done. Assessments of predictors of immediate periprocedural success was based on degree of clot lysis and resolution of symptoms and signs. Incidence of postthrombotic syndrome (PTS) was calculated at 6 months postoperative using Villalta score (≥5 vs <5). Results: During the study duration, 20 patients (22 limbs) were recruited. The mean age was 40.95 ± 12.35 years old, 11 patients (12 limbs) were women. The indication for CDT was severe progressive pain/swelling (18 limbs), and phlegmasia cerulea dolens (4 limbs). 5 patients (7 limbs) had IVC thrombosis at the initial venography. 5 limbs had balloon dilatation only while iliac stenting was done in 12 limbs. 15 patients received CDT for 48 hours while 5 patients (7 limbs) received CDT for 24 hours (mean duration of CDT was 1.68 days). As regards bleeding, only 2 cases of those who had CDT for 24 hours had bleeding, while bleeding occurred in 12 cases of those who had CDT for 48 hours. There were no recurrent DVT, intra or postoperative pulmonary embolism nor death within the study population till the end of the follow up period (6months). 6 months post intervention, 7 limbs were free of PTS (Villalta score < 5), 15 limbs had mild to moderate PTS, and no patients had severe PTS. The mean Villalta score was 5.14 ± 1.859. Conclusion: In our study, determinants of outcome following CDT for acute IFDVT were: 1) access site, 2) dose of thrombolytic agent used, 3) duration of thrombolysis, and 4) thrombus score at the end of the procedure. Mo...