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Abstract The use of regional citrate anticoagulation (RCA) in liver failure (LF) patients can lead to citrate accumulation. We aimed to evaluate serum levels of citrate and correlate them with liver function markers and with the Cat/Cai in patients under intensive care and undergoing continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA). A prospective cohort study in an intensive care unit was conducted. We compared survival, clinical, laboratorial and dialysis data between patients with and without LF. Citrate was measured daily. We evaluated 200 patients, 62 (31%) with LF. Citrate was significantly higher in the LF group. Dialysis dose, filter lifespan, systemic ionized calcium and Cat/Cai were similar between groups. There were weak to moderate positive correlations between Citrate and indicators of liver function and Cat/Cai. The LF group had higher mortality (70.5% vs. 51.8%, p = 0.014). Citrate was an independent risk factor for death, OR 11.3 (95% CI 2.74–46.8). In conclusion, hypercitratemia was an independent risk factor for death in individuals undergoing CVVHDF-ARC. The increase in citrate was limited in the LF group, without clinical significance. The correlation between citrate and liver function indicators was weak to moderate.