Faced with expectations to improve patient safety and contain costs, the US health care system is under increasing pressure to comprehensively and objectively account for nosocomial infections. Widely accepted nosocomial infection surveillance methods, however, are limited in scope, not sensitive, and applied inconsistently. In 907 inpatient admissions to Evanston Northwestern Healthcare hospitals (Evanston, IL), nosocomial infection identification by the Nosocomial Infection Marker (MedMined, Birmingham, AL), an electronic, laboratory-based marker, was compared with hospital-wide nosocomial infection detection by medical records review and established nosocomial infection detection methods. The sensitivity and specificity of marker analysis were 0.86 (95% confidence interval [CI 95], 0.76-0.96) and 0.984 (CI 95, 0.976, 0.992). Marker analysis also identified 11 intensive care unit-associated nosocomial infections (sensitivity, 1.0; specificity, 0.986). Nosocomial Infection Marker analysis had a comparable sensitivity (P > .3) to and lower specificity (P < .001) than medical records review. It is important to note that marker analysis statistically outperformed widely accepted surveillance methods, including hospital-wide detection by Study on the Efficacy of Nosocomial Infection Control chart review and intensive care unit detection by National Nosocomial Infections Surveillance techniques.