Post-thrombotic syndrome (PTS) is a complication that can develop after deep vein thrombosis (DVT) of lower extremities. In this meta-analysis, we compare the different modalities for treatment of DVT in reducing the risk of PTS. The primary outcome was the risk of PTS, and the secondary outcome included the risk of bleeding events. Review Manager (version 5.3; Cochrane Collaboration software) was used to analyze the data that are represented as a forest plot. Meta-analysis indicated that catheter-directed thrombolysis (CDT) plus anticoagulation (AC) decreases the likelihood of developing PTS compared with the AC-only group with an odds ratio of 0.28 (0.12-0.64). A subgroup analysis of randomized control trial (RCT) studies was conducted, and findings suggest a slight decrease in the likelihood of PTS incidence in the CDT+AC treatment group compared to the AC treatment group (odds ratio, OR = 0.76; CI = 0.58-0.99). For the secondary outcome, a statistically significant increase in bleeding events in the intervention groups was reported with an OR of 3.38 (1.33-8.61), suggesting that the risk of bleeding was high in the CDT plus AC group. CDT in addition to conventional AC for patients with DVT decreases the likelihood of PTS development. The protective effect of CDT comes at the expense of an increase in bleeding risk by three-fold. The decision to utilize CDT to prevent PTS should be individualized according to patient risk factors for developing PTS and their risk of bleeding.