The use of novel oral anticoagulants in patients with impaired renal function or undergoing immunosuppressive therapy is limited due to the risk of drug-to-drug interactions and anticoagulation-related adverse events. This article aims to assess the current data on the safety of direct-acting oral anticoagulant-based therapy in the population of kidney transplant recipients and patients with impaired renal function. The most important factors affecting the safety of treatment are the incidence of bleeding events, thromboembolic events, deaths and drug-to-drug interactions. The available data were compared to the findings on warfarin-based anticoagulation. Findings on the use of novel oral anticoagulants in kidney transplant recipients are limited yet promising in terms of safety and efficacy of use. However, current recommendations state that the co-administration of non-vitamin K antagonist oral anticoagulants with several immunosuppressive agents is contraindicated.