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Objectives: To study the role of ascitic fluid (AF) lactoferrin as a surrogate marker for the diagnosis of spontaneous bacterial peritonitis (SBP). Background: SBP is one of the most dangerous and life-threatening complications of liver cirrhosis and ascites. Its diagnosis is difficult, operator dependent, and time consuming. Materials and methods: This study was conducted on 60 patients with decompensated chronic liver disease and ascites admitted to the Tropical Medicine Department at Menoufia University Hospital. These patients were classified into two groups: group I (non-SBP group) and group II (SBP group). AF samples from both groups were examined for polymorphonuclear leukocyte cell count, AF culture, and lactoferrin levels. Results: The results showed a highly significant increase in AF lactoferrin in the SBP group and at a cut-off level of 255 ng/ml; the sensitivity and specificity of AF lactoferrin in the diagnosis of SBP were 100 and 88.9%, respectively. AF culture revealed the presence of organisms in 43.4% of patients in the SBP group; all organisms were gram negative. Conclusion: Our results support that AF lactoferrin could be used as a marker for screening and diagnosing SBP in patients with cirrhosis and ascites.