BACKGROUND. The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. METHODS. Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. RESULTS. During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line-days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001 ), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P=.018 ), and that sought to remove unneeded catheters increased from 37% to 83% (P=.004); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). CONCLUSIONS. Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years. © 2010 by The Society for Healthcare Epidemiology of America. All rights reserved.