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BACKGROUND: Treatment of intra-abdominal sepsis with antibacterial drugs should be initiated as soon as possible diagnosis is made before surgery and continued in the post operative period, unless required to be changed (when there is no satisfactory clinical response). The ideal agent (s) and duration of therapy remains somewhat controversial. However, early experimental and subsequent clinical studies have indicated that the spectrum of chosen antibacterial activity must encompass both colonic aerobes and anaerobes including B. fragilis. There are a number of multi drug protocols that are used to treat intra-abdominal septic conditions. Empiric use of these protocols not only adds toxicity to already ill patient but therapy becomes costly and utilizes human resource, unnecessarily. AIM OF STUDY: To study the clinical efficacy of the treatment of intra-abdominal sepsis with protocol -A (Ceftriaxone, Metronidazole and aminoglycoside) versus protocol -B. (Ceftriaxone and Metronidazole). MATERIAL AND METHODS: This is a prospective randomized study conducted at NGMC, Nepalgunj, Nepal (2003-2004) on the patient attending for the treatment of intra-abdominal sepsis. Patients included in this study were of inflammation, obstruction with or without gangrene and perforation of appendix, small bowel and large bowel with localized or generalized peritonitis. These patients were managed surgically by- appendicectomy, closure of perforation, resection and anastomosis (R & A) and resection and proximal colostomy. Patients of large bowel obstruction without gangrene and small bowel gangrene were managed by R & A. These patients had significant faecal spillage at the surgical site as well as in the peritoneum. At the end of operation peritoneum and surgical site of all cases were washed with saline and povidone-iodine solution. They were put on one of the two protocols for post-operative treatment. A total 59 patients were included in this study. 32 cases were treated with protocol- A and rest 27 cases were treated with protocol- B. These cases were selected randomly for this study. Their outcome was compiled and compared under following headings: postoperative recovery, postoperative pyrexia, wound infection and dehiscence, anastomotic leak, residual abscess and cost of therapy. STATISTICAL ANALYSIS: Statistical analysis was done with the help of Chi square test. RESULT: Of the 59 patients, 32 were randomized to group I, 27 to group II. These groups were comparable in age, weight, sex and duration of therapy. Uneventful recovery was noted in 87.5 % (28/32) in -group I where as in 70.37% (19 /27) in-group II. Complications were observed in 12.5% in-group I where as 29.63 % in-group II. 10 patients in-group I where as 7 patients in -group II had surgical site infections (SSIs). All of these had superficial wound infection with/or without dehiscence of small portion of wound. A single case of residual abscess and anastomotic leak was observed. Postoperative pyrexia was noted in 8 patients in-group I where as in 6 patients in-group II. In pyrexia, temperature ranged from 99-104 0F. Finally except one case, rest of the cases recovered. On follow up after 3weeks, the cases recovered were doing well. CONCLUSION: At least three conclusions can be drawn from this study. Firstly protocol A is equally effective as protocol B. Secondly; it appears that combining aminoglycoside with Ceftriaxone therapeutically has no significant (P = 0.09) benefit over Ceftriaxone alone. Finally protocol A is less expensive in terms of total therapy than protocol B and can be used without fear even in subnormal functioning kidney.