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The use of enoxaparin is generally not recommended in patients with end-stage renal disease (ESRD) and undergoing haemodialysis. We describe the administration of high-dose enoxaparin in a haemodialysis patient with heparin resistance and recurrent deep vein thrombosis (DVT) outlining a novel dosing regimen along an innovative method for monitoring antifactor Xa activity. As a last resort of his recurrent DVT, a critically ill intensive care unit patient undergoing dialysis was prescribed high-dose enoxaparin, administered exclusively after dialysis, on dialysis days for a period of 2 months. Antifactor Xa activity was measured 4 hours postadministration with a target range of 0.7–1.2 IU/mL. The patient’s DVT demonstrated clinical improvement, antifactor Xa levels were maintained within the therapeutic range and haemoglobin levels remained stable with no signs of bleeding. This case reports the implementation of a high-dose enoxaparin dosing and monitoring strategy in a high-risk patient. However, further studies involving larger patient cohorts are required to validate this approach.