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Introduction Ascitic fluid infection (AFI) is a serious complication in patients with decompensated liver disease with a mortality approaching 30%.Third generation cephalosporin (TGC) have been effectively used for this infection. However resistance has been increasing it is therefore imperative to define the effectiveness of TGC for AFI.Material and Methods This cross sectional study was conducted on consecutive subjects with AFI who received of injection Ceftriaxone from January 2021 till September 2025 at The Indus Hospital and Health Network, Karachi. AFI was diagnosed based on ascitic fluid Polymorph nuclear count (PMN) of 250 cells/mm 3 and or positive ascitic fluid culture. All patients had a repeat diagnostic tap of ascitic fluid 48 hours after the index tap. Failure of reduction of PMN count in the latter tap and/or ascitic fluid bacteria resistant to TGC were considered as nonresponders. Patients receiving any other antibiotic, prior documented resistance to TGC and patients with hepatoma were excluded.Results We enrolled total of 223 patients with AFI received TGC during the study period and were analyzed. Out of them 123(55.2%) were males. Hepatitis C was the commonest etiology in 151 (67.7%) and 185(80.8%) were in Child class C. Total of 175(78%) responded to TGC while 48(22%) were nonresponders. Ascitic fluid culture was positive in 51(22.9%) patients. The predominant organism found in ascitic fluid was E.Coli in 27(53%) of the culture positive group.147 (85%) of cases amongst culture negative group responded as compared to 28(55%) of patients in culture positive group. On univariate analysis total bilirubin>6mg/dL, Prothrombin time >22 seconds and positive Ascitic fluid culture (p value 0.04, 0.02 and <0.001 respectively) were associated with non response to TGC. On multivariate analysis only ascitic fluid positivity was associated with non response to TGC.Conclusion We found 22% resistance to TGC in SBP. Positive ascetic fluid culture is independently associated with nonresponse to TGC.