PURPOSE: The optimal antibiotic regimen for appendicitis still remains poorly defined. The aim of this study was to define the optimal duration and route of antibiotics after an appendectomy, with regard to the clinicopathololgical aspects. METHODS: This study was performed on 73 consecutive patients who underwent an appendectomy. Groups A and B, which were composed of cases of simple appendicitis (phlegmonous and suppurative type) and complicated appendicitis (gangrenous and perforated type), respectively. Group A was randomized after the appendectomy into either A1 (n=17), a 1-day course of a combination of IV first generation cephalosporin and tobramycin; or to A2 (n=26), a 3-day course of the same regimen. Group B was randomized into either B1 (n=16), a 3-day course of a combination of IV cephalosporin, tobramycin, and metronidazole, followed by conversion to a 4-day course of a combination of PO third generation cephalosporin and metronidazole; or B2 (n=7), a 7-day course of a combination of IV cephalosporin and metronidazole, along with a 5-day course of tobramycin. The total leukocyte count (WBC), neutrophil count, and C-reactive protein (CRP) were analyzed preoperatively and on POD #3 and #7. An intraoperative culture of the surface of the appendix was also performed. RESULTS: The most common cultured organism was Escherichia coli (n=30). Ampicillin and first generation cephalosporin were 73% and 49% resistant to Gram-negative organisms, respectively. Third generation cephalosporin and imipenem were 100% sensitive. The subjects in group A were all under normal limits in the postoperative laboratory analyses, and had no complication. Groups B1 and B2 showed no significant differences in their WBC (P=0.301), neutrophil count (P=0.730), and complications (P=0.907), with the exception of CRP (P=0.040). CONCLUSION: After the appendectomy, simple appendicitis was treated with antibiotics for 24 hrs, with no complications. For complicated appendicitis, a 3-day IV course, followed by a conversion to 4-day PO antibiotics, was found to be safe. Surveillance of the WBC and neutrophil counts, CRP values, and body temperature permitted safe utilization of this regimen.