The aim of this study is to identify the antibiotic sensitivity pattern of pathogens involved in the process of surgical site infection, in surgical wards. Changes made in the pattern of antibiotic use will result in different microorganism susceptibility patterns, which needs correct determination for precise empiric antibiotic therapy. One thousand patients (62% men and 38% women, 18- 74-years-old, with mean age 43 +/- 8)) who underwent surgical treatment, in Alzahra University Hospital, Isfahan University of Medicine, Isfahan, Iran, were studied from 2005 to 2006. Surgical wound infections, based on the reported criteria, were aspirated for culturing within 1 plus gram staining of prepared smears. Minimum Inhibitory Concentrations (MICs) were determined for samples and all derived data were compared by SPSS 13 and WHO net 5 software. The prevalence of SSI was 13.3% with 150 positive cultures, totally. Of 150 bacteria, isolated from surgical site infections Staphylococcus aureus had most frequency (43%). Resistance of isolated organisms was 41.7% in amikacin, 65 and 78.6% in ceftazidime, 85.7% in ceftriaxone, 61.5% in ciprofloxacin, 78.8% in gentamicine, 6.4% in imipenem, 13% in meropenem and 70.6% in trimethoprim/sulfamethoxazole, respectively. 78.9% of Staphylococcus aureus isolates were MRSA and vancomycine was the most effective antibiotic without any resistance. Among 10 isolates of coagulase negative Staphylococcus, no vancomycine resistance was seen, but in contrast all cases were resistant to oxacillin. The most common gram negative organism was Klebsiella (18 isolates) in which 100 and 80% were sensitive to imipenem and meropenem, respectively. Seventeen cases were E. coli, in which the most sensitivity was to meropenem (80%) and imipenem (77.8%). Thirteen cases of Pseudomonas were detected, in which 16.7% were resistant to imipenem and 8.3% to meropenem. Our results demonstrated that the total antibiotic resistance is increasing among SSIs, with an up sloping pattern, which will contact with a constant empiric antibiotic therapy. So, precise up to date antibiogram tantalize us toward balancing the rate of total antibiotic resistance to SSIs.