Background: The presence of an elevated absolute polymorphonuclear leukocyte count in the ascitic fluid (>250 cells/mm3) in combination with a positive ascitic fluid bacterial culture is diagnostic of spontaneous bacterial peritonitis. Among the families of calcium-binding proteins known as S100, calprotectin belongs to the subfamily known as calgranulins. Objective: The aim of the current work was to examine the value of ascitic fluid calprotectin for the diagnosis and prognosis of spontaneous bacterial peritonitis in people with liver cirrhosis. Patients and Methods: Between April 2018 and May 2019, 50 Egyptians with liver cirrhosis and ascites were recruited. Forty individuals with spontaneous bacterial peritonitis (SBP) and 10 patients with ascites without SBP were studied. Biochemical, bacterial, and ascitic calprotectin level, as well as diagnostic paracentesis, were performed to all patients. Results: When comparing individuals with cirrhosis and SBP to those without SBP, the level of calprotectin in the ascitic fluid was significantly higher in SBP patients (P= 0.000). Its mean values were statistically significantly reduced after treatment of SBP in comparison to its level before treatment [reduced from 626.75 ± 188.05 to 251.25 ± 223.13 ug/l] with p value 0.000. At a cutoff value of >320 ug/l, ascitic calprotectin may be a possible marker of development of SBP among cirrhotic patients with ascites with 95% sensitivity and 90% specificity. Conclusion: It could be concluded that ascitic fluid calprotectin may be useful in the diagnosis and prognosis of patients with liver cirrhosis and spontaneous bacterial peritonitis.