Metformin associated lactic acidosis (MALA) and severe acute kidney injury (AKI) is a life-threatening condition, often requiring renal replacement therapy. However, the optimal renal replacement therapy regimen in this setting remains unclear. Furthermore, limited data exist on the use of regional citrate anticoagulation, as severe hyperlactatemia is associated with increased risk of citrate accumulation. We retrospectively analyzed the medical records of all patients with MALA and severe AKI requiring renal replacement therapy at our hospital between June 2011 and December 2021. All patients were treated with high dose CVVHDF. Anticoagulation was achieved using either heparin or regional citrate anticoagulation. A total of 27 patients with MALA and AKI requiring renal replacement therapy were identified. In all patients, CVVHDF was started within one hour of the diagnosis. Four deaths were recorded, resulting in an overall mortality rate of 14.8%. In the remaining 23 patients (85.2%), we observed the correction of the metabolic disorder and the recovery of renal function that allowed for the discontinuation of dialysis. Mean lactatemia at diagnosis was 12.9 mmol/l (range 7.0-24.0) and mean pH 6.99 (range 6.50-7.22). CVVHDF mean effluent rate was as high as 52.1 ml/kg/h. In thirteen patients regional citrate anticoagulation was safely employed. In our experience, CVVHDF prescribed at the appropriate dose have yielded favorable results, in terms both of patient survival and metabolic control of the disease. Regional citrate anticoagulation can be safely used in selected cases.