Background: Spontaneous bacterial peritonitis (SBP) is an acute bacterial infection of ascitic fluid. Generally, no source of the infecting agent is easily identifiable. The aim of this work was to identify the most suitable antibiotic to describe for empiric therapy of spontaneous bacterial peritonitis (SBP) in Egyptian patients with liver cirrhosis and ascites. Methods: This study was carried out on 80 cirrhotic patients from Benha university hospitals and Ahmed Maher Teaching hospital underwent ascetic fluid analysis for PMN cell count and culture\sensitivity, Thorough history taking, full general and local examination, full investigations, serological tests for viral markers, modified Child's Pugh classification, abdominal ultrasonography and diagnostic abdominal paracentesis.Results: PMN cell count of all studied patients was over 250 cells/µL, 30 patients (37.5%) their culture were negative (no growth organisms) which is a large variant of SBP called culture negative neutrocytic ascites,50 patients (62.5%) their culture was positive. For gram stain negative organisms 41 patient (82%), E. coli (53.66%) mostly sensitive to cefotaxime (80%), ceftriaxone (87.50%), cefoperazone (76.92%), out of the 22 E. coli 4 (18.18%) were multidrug resistant, 3 (13.64%) were extensive drug resistant. For gram stain positive organisms 9 (18%), Staphylococcus aureus (77.78%) mostly sensitive to trimethoprim\sulphamethoxasole (100%), vancomycin (85.7%), linezolid (100%), out of 5 staphylococcus aureus 4 (57.14%) were multidrug resistant, 1 (20%) was extensive drug resistant.Conclusion: If PMN cell count more than 250 cells/µL should start empirical third generation cephalosporin antimicrobial treatment for 10 to 14 days even if culture\sensitivity result is negative. Amikacin & cefepime should be considered in empirical antimicrobial therapy in spontaneous bacterial peritonitis with dose adjustment according to creatinine clearance.