Objective: Effective treatment for acute limb-threatening lower extremity (LE) thrombosis involves thrombolysis in addition to anticoagulation. There is limited available data on the outcomes and safety of catheter directed thrombolysis (CDT) to help guide its use in pediatrics. Procedure: Single-center retrospective medical record review of children (<21 years of age) that received CDT for LE and inferior vena cava (IVC) thrombosis over a 5-year span at a pediatric tertiary care center. Results: A total of 29 patients were identified for inclusion in the study, 76% (n=22) received overnight CDT while 24% (n=7) received tissue plasminogen activator (tPA) as a bolus dose during a single interventional procedure. The median age of the cohort was 15.8 years (range 0-19.1). All patients were treated with a course of anticoagulation. The thromboses represented were extensive, with 93% (n=27) being occlusive and affecting multiple venous segments. Thrombus resolution occurred in 35% (n=10) of patients. Rivaroxaban use during the course of anticoagulation and estrogen-containing hormonal therapy use prior to diagnosis were associated with thrombus resolution, while Hispanic ethnicity was associated with thrombus persistence. There was one major and 3 minor bleeding events that occurred as a complication of thrombolysis and no treatment related deaths. Conclusions: The administration of tPA, whether by CDT or as an intra-procedural bolus, for extensive LE and IVC thromboses is effective and safe in children when combined with a course of anticoagulation.