Objective: We assessed the impact of an extended-spectrum antibiotic prophylaxis regimen (azithromycin in addition to recommended narrow-spectrum cephalosporin) on postcesarean incisional wound infection. Study Design: Data from prospective surveillance of surgical site infections at our institution were used to compare incidence in postcesarean incisional wound infection for 3 consecutive time periods of antibiotic prophylaxis: (1) standard (ie, cephalosporin only, 1992-1996); (2) clinical trial of extended spectrum (ie, extended vs cephalosporin only, 1997-1999); and (3) routine use of extended spectrum (2001-2006). Results: The incidence of postcesarean incisional wound infections decreased progressively from 3.1% to 2.4% and then to 1.3% over the 3 consecutive periods (P value for trend < .002). Conclusion: Increasing the use of extended-spectrum antibiotic prophylaxis at our institution over 3 time periods was associated with a decreasing trend in postcesarean incisional wound infection. © 2008 Mosby, Inc. All rights reserved.