Rivaroxaban used for treating cancer-associated venous thromboembolism (Ca-VTE) may be associated with major bleeding events (MBEs) and VTE-recurrences. A few studies were focused on its use in renally compromised cancer patients. This study aimed to assess the therapeutic efficacy and clinical safety of rivaroxaban vs. enoxaparin in Ca-VTE patients with and without renal impairment. An analysis on fixed-oral-dose rivaroxaban versus traditional enoxaparin was performed in terms of clinical safety and therapeutic efficacy in Ca-VTE diagnosed patients of either group i.e., with and without renal impairment at Shaukat Khanum Memorial Cancer Hospital & Research Centre, Peshawar, enrolled from 2016 to 2020. Primary safety and efficacy outcomes were MBE and VTE-recurrence respectively, assessed at baseline and after 3 months of treatment. Among 100 patients, 50% received rivaroxaban and remaining 50% enoxaparin treatment. Higher MBE rate was associated with enoxaparin vs. rivaroxaban treated arm with an insignificant difference (10% vs. 4%; 95% CI; P=0.09). However, rivaroxaban users had a higher but insignificant VTE-recurrence rate as compared to enoxaparin users (32% vs. 20%; 95% CI; P=0.23). The overall rate of MBEs and VTE recurrence was comparatively higher in renally impaired patients. Conclusively, the study revealed that the risk of recurrent VTE and MBE increases with a corresponding alteration in renal function of Ca-VTE patients. In treating Ca-VTE (with or without renal impairment), rivaroxaban may be a better alternative to enoxaparin with high safety and of comparable efficacy profile. Drug dosage adjustment plays a significant role in reducing the risk of bleeding with enoxaparin.