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This study aimed to evaluate the safety and efficacy of a regional citrate anticoagulation (RCA) protocol for continuous venovenous hemodialysis (CVVHD) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) setting.One hundred twenty two consecutive ICU cancer patients with AKI treated with citrate-based CVVHD were prospectively evaluated in this prospective observational study.A total of 7198 h of CVVHD therapy (250 filters) were performed. Patients were 61.3 ± 15.7 years old, 78% had solid cancer and the main AKI cause was sepsis (50%). The in-hospital mortality was 78.7%. Systemic ionized calcium (SCai) was 4.35 (4.10–4.60) mg/dL, severe hypocalcemia (SCai <3.6 mg/dL) was observed in 4.3% of procedures and post-filter ionized calcium was 1.60 (1.40–1.80) mg/dL. Median filter patency was 24.8 (11–43) hours. Factors related to filter clotting were: no tumor evidence (OR 0.44, CI 0.18–0.99); genitourinary tumor (OR 1.83, CI 1.18–2.81); platelets number (each 10,000/mm3) (OR 1.02, CI 1.00–1.04); International Normatized Ratio (INR) (OR 0.59, CI 0.41–0.85) and citrate dose (each 10 mL/h) (OR 0.88, CI 0.82–0.95).Filter patency was relatively short and clotting was associated with active cancer disease, genitourinary tumor, lower citrate dose and lower INR.Regional citrate anticoagulation was safe and associated with adequated metabolic control.The incidence of electrolytic and acid-base disorders was similar to that observed in non cancer patients.Filter patency was relatively short 24.8 (11 – 43) hours.Factors related to filter clotting were, genitourinary tumor, platelets number and citrate dose.