Background: The dissemination of resistant strains of bacteria into the environment through hospital sewage has been recognized as a public health concern. We investigated the antibiotic resistance profile of E. coli isolated from hospital sewage.Methods: E. coli strains were isolated from the hospital sewage system from both pre and post treatment phases in a general hospital of Kermanshah city (west of Iran). Resistance to antibiotics (clindamycin, ceftriaxone, Co-trimoxazole, penicillin, ciprofloxacin, amikacin, gentamicin, imipenem, and piperacillin) was determined by disc diffusion. Isolates were screened phenotypically for extended-spectrum beta-lactamases (ESBL) production. The frequency of common antibiotic resistance genes (bla CTX-M, bla TEM, bla SHV, and qnr) were detected by PCR and data was statistically analyzed.Results: Sixty E. coli strains (30 for pre treatment and 30 for post treatment sewage) were randomly selected from isolates. All ESBL-producing isolates showed resistance to three antibiotic classes and were MDR. For non-ESBL isolates, 70 and 90 percent were MDR for pre and post treatment sewage, respectively. Of isolates tested, 100% had at least one of resistance genes. The frequency of bla CTX-M-1 gene was significantly higher in isolates of post treatment sewage. The bla TEM gene was more common than other genes in ESBL-producing isolates.Conclusion: The high rate of antibiotic resistance and resistance genes in E. coli isolates of hospital sewage, especially in post treatment is alarming. These data suggest that despite the widespread use of active sludge system to treat hospital sewage, they may not capable to adequately eliminate or reduce the antibiotic resistance strains of E.coli.