Introduction: We conducted an 8-month prospective single-center observational study in patients with acute kidney injury treated with continuous veno-venous hemofiltration (CVVH) to compare the impact of two citrate formulations on filter lifespan (FLS). Methods: Patients received CVVH at a delivered dose of 25 ml/kg/h. Multivariable linear regression was performed to assess the influence of different variables on circuit lifespan. Results: We included 59 patients, 28 received the 10/2 formulation and 31 received the 18/0 formulation. Median (interquartile range) FLS was significantly prolonged with the 18/0 solution compared with the 10/2 solution (4.10 (2.45-5.75) vs. 2.68 (0.47-4.99) days, p = 0.001). No confounding variables (difference in ionized calcium target, citrate flow or dose, platelet count, hematocrit, vascular access location) affecting filter capacity or lifespan between the 2 formulations were identified. Conclusions: Under similar conditions of CVVH and calcium targets, a Prismocitrate 18/0 formulation significantly improved FLS as compared with Prismocitrate 10/2.