Nasal carriage of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) is associated with an increased risk for postoperative staphylococcal infection. This study was conducted to investigate the effect of preoperative nasal mupirocin treatment on the postoperative infections in patients undergoing upper gastrointestinal surgery. The intervention group consisted of 141 consecutive patients who underwent upper gastrointestinal surgery between March 1, 1997, and February 28, 1998. The patients in the intervention group were treated with intranasal mupirocin three times a day for 3 consecutive days before surgery. The incidence of postoperative staphylococcal infections in the intervention group was then compared with that of the historical control group. The control group consisted of 128 consecutive patients who underwent upper gastrointestinal surgery without mupirocin treatment between January 1, 1996 and December 31, 1996. The postoperative staphylococcal infection rate in the control group (11.7%) was significantly higher (P < 0.001) than in the intervention group (0.71%). The postoperative MRSA infection rate was significantly reduced by the intervention (control group 7.0% and intervention group 0%; P < 0.01). These results suggest that preoperative nasal eradication of S. aureus with mupirocin thus appears to be an effective measure to prevent postoperative staphylococcal infection in patients undergoing upper gastrointestinal surgery.