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OBJECTIVE To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and the INICC Surveillance Online System (ISOS) on central line-associated bloodstream infection (CLABSI) rates in 14 intensive care units (ICUs) in Argentina from January 2014 to April 2017. DESIGN This prospective, pre-post surveillance study of 3,940 ICU patients was conducted in 11 hospitals in 5 cities in Argentina. During our baseline evaluation, we performed outcome and process surveillance of CLABSI applying Centers for Disease Control and Prevention/National Health Safety Network (CDC/NHSN) definitions. During the intervention, we implemented the IMA through ISOS: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on CLABSI rates and consequences, and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using a logistic regression model to estimate the effect of the intervention on the CLABSI rate. RESULTS During the baseline period, 5,118 CL days and 49 CLABSIs were recorded, for a rate of 9.6 CLABSIs per 1,000 central-line (CL) days. During the intervention, 15,659 CL days and 68 CLABSIs were recorded, for a rate of 4.1 CLABSIs per 1,000 CL days. The CLABSI rate was reduced by 57% (incidence density rate: 0.43; 95% confidence interval, 0.34-0.6; P<.001). CONCLUSIONS Implementing IMA through ISOS was associated with a significant reduction in the CLABSI rate in ICUs in Argentina. Infect Control Hosp Epidemiol 2018;39:445-451.