Safety of Direct Oral Anticoagulants (DOAC) in Cancer Associated Thrombosis (CAT) in patients with Gastrointestinal (GI) and Genito-Urinary (GU) malignancies is uncertain. We identified patients with active GI and GU malignancies who received either enoxaparin or a DOAC (apixaban or rivaroxaban) for CAT from July 2001 to July 2020. Demographics, disease characteristics, thrombosis data, date of anticoagulation initiation, and bleeding events at one year were recorded and analysed. We identified 206 patients, 159 received DOAC (86 apixaban; 73 rivaroxaban) and 47 enoxaparin; 128 (62.1%) and 78 (37.9%) had GI and GU malignancies, respectively. Choice of anticoagulation varied significantly based on primary malignancy. Enoxaparin was preferred in GU tumors while DOACs were preferred in GI tumors (p=0.014). Within DOACs, rivaroxaban use was higher with GI cancers and apixaban was prescribed more often in GU malignancies (p=0.00049). Anticoagulated associated bleeding events in GI and GU cancers were common (22.2%). No difference in bleeding events was observed between enoxaparin (21.7%) and DOACs (22.4%) in patients with GI (p=0.56) or GU (p=0.74) tumors or for the combined CAT group (p=0.93). Apixaban and rivaroxaban had similar bleeding event rates. The majority of patients who experienced a bleeding event, 28/44 (63.6%), bled at the cancer site with a trend for increased bleeding in GU cancer patients on DOACs vs. enoxaparin (p=0.089). Anticoagulated associated bleeding in GI and GU cancers are common with enoxaparin and DOACs. There is a high percentage of bleeding at the tumour site in both malignancies irrespective of anticoagulant agent.