Context: Catheter-directed thrombolysis (CDT) is a novel mode of thrombolysis where thrombolytic agents are directed through catheter to a specific area of interest; hence, low-dose thrombolytic agent will be required to produce satisfactory thrombolysis results. This will subsequently decrease the bleeding complications. With this postulation, a study was conducted to compare the outcome of CDT versus systemic thrombolysis (ST) in patients with massive and submassive pulmonary embolism (PE). Methods: The present study prospectively included the cases of massive and submassive (high-risk) PE and randomly distributed 25 patients into two groups each: Group A underwent CDT, whereas Group B underwent ST. The outcomes of both the groups were studied including mortality and bleeding complications, and patients were followed up for 6 months. At the end of the study, data were analyzed, and outcomes of both the groups were compared. Results: Baseline characteristics were similar in both the groups. The success rate was 90.4% in Group A (CDT) and 75% in Group B (ST) among patients with massive PE (P = 0.95). The mortality rate was numerically higher in the ST group (12%) than in the CDT group (8%). Bleeding complications were higher in the ST group (20%) than in the CDT group (8%). Conclusion: CDT was found to be noninferior to ST with respect to primary outcomes of mortality and success rate of thrombolysis. CDT had lower occurrence of bleeding episodes. CDT can be considered viable alternative to ST in patients with high bleeding risk.