OBJECTIVETo develop a probabilistic method for measuring central line–associated bloodstream infection (CLABSI) rates that reduces the variability associated with traditional, manual methods of applying CLABSI surveillance definitions.DESIGNMulticenter retrospective cohort study of bacteremia episodes among patients hospitalized in adult patient-care units; the study evaluated presence of CLABSI.SETTINGHospitals that used SafetySurveillor software system (Premier) and who also reported to the Centers for Disease Control and Prevention’s National Healthcare Safety Network (NHSN).PATIENTSPatients were identified from a stratified sample from all eligible blood culture isolates from all eligible hospital units to generate a final set with an equal distribution (ie, 20%) from each unit type. Units were divided a priori into 5 major groups: medical intensive care unit, surgical intensive care unit, medical-surgical intensive care unit, hematology unit, or general medical wards.INTERVENTIONSEpisodes were reviewed by 2 experts, and a selection of discordant reviews were re-reviewed. Data were joined with NHSN data for hospitals for in-plan months. A predictive model was created; model performance was assessed using the c statistic in a validation set and comparison with NHSN reported rates for in-plan months.RESULTSA final model was created with predictors of CLABSI. The c statistic for the final model was 0.75 (0.68–0.80). Rates from regression modeling correlated better with expert review than NHSN-reported rates.CONCLUSIONSThe use of a regression model based on the clinical characteristics of the bacteremia outperformed traditional infection preventionist surveillance compared with an expert-derived reference standard.Infect. Control Hosp. Epidemiol. 2016;37(2):149–155