Background Catheter-directed thrombolysis (CDT) for acute iliofemoral deep venous thrombosis (DVT) is an endovenous interventional therapy that can quickly remove the acute thrombus, thereby improving the clinical outcomes of proximal DVT. However, instrumentation of extensive fresh thrombus may be associated with iatrogenic pulmonary embolism (PE). Therefore, we aimed to compare CDT’s safety, complications, and perioperative embolic (PE) insults for acute iliofemoral DVT, with and without an IVC filter. Methods One hundred twenty patients having acute proximal DVT for less than 14 days and undergoing endovenous therapy were included and presented to the vascular surgery department of Al-Azhar University Hospitals, Egypt. The patients were randomized into two equal groups, Groups A and B, each having 60 patients. Group A was treated with IVC filter insertion, while Group B was treated without a filter. The anticoagulation and CDT procedures were similar between the two groups. Results The sample included 96 females (80%) and 24 males (20%), with a mean age of 32.6 ± 7.2 years. Clinically no clinical PE occurred in both groups. However, radiologically, new lesions in multislice CT pulmonary angiogram and V/Q scan were noted in two of 60 patients (3.33%) of the IVC filter group, compared with three patients (5 %) in the non-filtered group. Conclusion Endovenous intervention in the form of CDT for acute iliofemoral DVT without an IVC filter is safe and not associated with an increased risk of pulmonary embolization than filter usage. The routine use of IVC filters should not be used mandatorily during CDT.