Objectives Low-molecular weight heparin (LMWH) has been approved for treatment of deep venous thrombosis and venous thromboembolism which are associated with cancer. The efficacy and safety of apixaban in management of acute deep venous thrombosis associated with active malignancy is still an unresolved issue. The aim of our study is to evaluate the efficacy and safety of apixaban in patients with acute deep venous thrombosis and active malignancy compared with weight adjusted subcutaneous LMWH. Methods Of 138 randomized patients, 100 patients with active malignancy presenting with acute deep venous thrombosis and still treated with chemotherapy were assigned to either oral apixaban therapy or subcutaneous low-molecular weight heparin (enoxaparin) through randomized clinical study in 1:1 ratio. All patients were followed up to six months. The primary end point was major bleeding, while secondary end points were recurrent deep venous thrombosis or venous thromboembolism, minor or non-fatal bleeding and mortality related to massive pulmonary embolism. Results Both groups were matched regarding their baseline demographic, clinical and laboratory characteristics. We had 84 patients with metastatic cancer (stage 4). The most prevalent type of malignancy was cancer colon (42% of cases). There was no significant difference between both groups regarding the incidence of primary and secondary end points. There were no reported mortality cases related to massive pulmonary embolism in both groups. Conclusion In this limited study, there was no difference in the major bleeding, recurrent deep venous thrombosis or minor bleeding in patients with active malignancy when treated with either apixaban or LMWH. Trial registration: ClinicalTrials.gov (NCT04462003). Registered 7 July 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04462003