OBJECTIVE: The purpose of this article is to compare the Charlson comorbidity index derived from a rapid single-day chart review with the same index derived from administrative data to determine how well each predicted inpatient mortality and nosocomial infection. DESIGN: Cross-sectional study. SETTING: The study was conducted in the context of the Swiss Nosocomial Infection Prevalence (SNIP) study in six hospitals, canton of Valais, Switzerland, in 2002 and 2003. PARTICIPANTS: We included 890 adult patients hospitalized from acute care wards. MAIN OUTCOME MEASURES: The Charlson comorbidity index was recorded during one single-day for the SNIP study, and from administrative data (International Classification of Disease, 10th revision codes). Outcomes of interest were hospital mortality and nosocomial infection. RESULTS: Out of 17 comorbidities from the Charlson index, 11 had higher prevalence in administrative data, 4 a lower and two a similar compared with the single-day chart review. Kappa values between both databases ranged from -0.001 to 0.56. Using logistic regression to predict hospital outcomes, Charlson index derived from administrative data provided a higher C statistic compared with single-day chart review for hospital mortality (C = 0.863 and C = 0.795, respectively) and for nosocomial infection (C = 0.645 and C = 0.614, respectively). CONCLUSIONS: The Charlson index derived from administrative data was superior to the index derived from rapid single-day chart review. We suggest therefore using administrative data, instead of single-day chart review, when assessing comorbidities in the context of the evaluation of nosocomial infections.