Background: Central-line–associated bloodstream infections (CLABSIs) increase the length of hospital stay, healthcare costs, and patient mortality. Objective: We conducted a quality improvement (QI) approach with plan-do-study-act (PDSA) cycle to strengthen adherence to a central-line (CL) maintenance bundle and to reduce CLABSI rate in a surgical intensive care unit (ICU) of children’s hospital 1 (CH1). Methods: The baseline CLABSI rate per 1,000 CL days and the ratio of CL days to patient days (device utilization ration; DUR) were captured for 12 months preceding the intervention. Baseline process indicators were captured for 2 months preceding implementation, including hand hygiene adherence, sterile technique for dressing change and CL access, CL hub cleaning, dating of CL components and daily chlorhexidine bathing. A multimodal intervention of clinician training, bedside checklist, and poster reminders of best practices was implemented. Process and outcome measures were monitored over 12 months of implementation. Z-test was used to calculate statistical significance before and after intervention. Results: Among 46 clinical ICU staff trained on a CLABSI maintenance bundle, mean pre- and posttest knowledge scores increased from 63% to 86%. Staff adherence to each CL care bundle element improved significantly (P < .001) and sustainably over the intervention period: hand hygiene adherence increased from 54% to 82%; sterile technique for dressing increased from 60% to 94%; sterile technique for CL access increased from 51% to 97%; hub scrubbing increased from 52% to 93%; dating of CL elements increased from 63% to 85%; daily chlorhexidine bathing increased from 52% to 87%. During the first 9 months, the CLABSI rate and the DUR decreased from 5.8 to 3.7 and from 0.43 to 0.41, respectively. In the following 2 months, the CLABSI rate increased to 12.7 while bundle adherence remained high. A root-cause analysis identified inadequate environmental hygiene and use of multidose saline bottles for multiple patients as potential factors. A PDSA cycle to improve these elements (enhanced cleaning; single-patient saline bottles) led to a decrease in the CLABSI rate from 12.7 to 3.0 after these efforts. Conclusions: This is the first time CH1 has used quality improvement methodology to implement an HAI prevention enhancement, which proved effective at creating and sustaining adherence to a multimodal CL maintenance bundle and an overall decrease in CLABSI rates. A 2-month increase in CLABSI rates highlights the unique challenges faced in low-resource settings and demonstrates the need for IPC elements not captured in a typical CLABSI prevention bundle. The quality improvement methodology provided a structured approach to implementing change. This methodology will be used for additional patient safety improvements at CH1 and other Viet Nam hospitals interested in CLABSI prevention.