OBJECTIVES: During the 1990's, colorectal patients in the U.S. experienced 6.5 extra hospital days and $3,089 in costs attributable to surgical wound infections, but no updated information is available. We utilized a large U.S. hospital database to identify the variables associated with increased length of stay (LOS) and costs for colon procedures. METHODS: We utilized a retrospective comparative national database to assess LOS and costs in 196 hospitals from 1/1/2005 through 6/30/2006. The study population was all patients >18 years, identified via ICD-9 & CPT procedure codes for elective colon procedures. Patients given cefotetan as surgical prophylaxis were compared to patients given commonly used prophylactic antimicrobials, including cefazolin/metronidazole. Patient demographics, surgical procedure, primary diagnosis, co-morbidities, and patient severity were examined as predictors of LOS <7 days and cost >=$15,000 using logistic regression. Patient severity was classified by APR-DRG severity of illness subclasses and SENIC risk index for infection. RESULTS: Hospitals were mostly urban (90%) with > 300 beds (70%), and 58% were non-teaching. They represented each region of the U.S., though predominantly Mid- and South-Atlantic (44.0). The 23,801 unique patients were 51% > 65 years, 53% female, and 73% white. The overall infection rate was 3.3%; mean LOS 7.0 (SD 5.7); mean total cost $12,871 (SD $11,295); and mean daily cost $2,015 (SD $917). In an adjusted model, compared to cefazolin/metronidazole, cefotetan is associated with a lower rate of LOS 7 days or more (OR=0.92; p=0.007) and total cost >=$15,000 (OR=0.71; p<0.001). Additional predictors of greater LOS and costs are elevated severity (OR=9.02 & 11.53) and SENIC scores (OR=1.51 & 4.12), age <75 (OR=2.18 & 1.66), and non-white ethnicity (OR=1.31 & 1.16). CONCLUSION: Cefotetan has limited availability and substitutions are increasingly utilized. Yet in elective colon procedures, cefotetan used as surgical prophylaxis is associated with lower LOS and costs compared to cefazolin/metronidazole.