Objective: To identify the microbial profile and susceptibility pattern of pathogens responsible for culture-proven postoperative endophthalmitis, and to investigate possible trends in both pathogens and antibiotic sensitivities., Methods: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised record of ophthalmology patients from January 1, 2005, to December 31, 2016. Culture and sensitivity reports of vitreous and aqueous humor samples from all the patients were retrieved from the medical record section of the hospital. SPSS 19 was used for data analysis., Results: Of the samples of 202 patients with a mean age of 58.2±15.8 years, 106(52.5%) were culturepositive. Of them, 55(51.8%) had gram-negative bacteria, 41(38.6%) had gram-positive bacteria, and 10(9.4%) had fungi. Among gram-positive bacteria, coagulase-negative staphylococcus was the principal isolate 18(17%) and among gram-negative bacteria, it was pseudomonas species 20(18.8%). Spectrum of gram-positive sensitivities included vancomycin 100%, gentamicin 91.5%, amikacin 100%, ciprofloxacin 68%, chloramphenicol 100%, and tetracycline 84.6%. Among gram-negative organisms, the sensitivities were ciprofloxacin 52.9%, ofloxacin 66.6%, ceftazidime 91.8%, amikacin 100%, tobramycin 100% imipenem 91.6%, gentamicin 81.2% and tetracycline 75%., Conclusions: Vancomycin and ceftazidime were the best empirical antibiotic selection to treat postoperative endophthalmitis.