Introduction Central-line–associated bloodstream infections (CLABSI) are preventable hospital-acquired infections that harm and prolong a patient's hospital stay and increase unnecessary hospital expenditure. In collaboration with infection control and hospital epidemiology, the quality management department initiated a performance improvement project to address 144 CLABSI events in 2017. Methods The performance improvement project team used brainstorming to create change ideas presented in a driver diagram. The team then applied plan-do-study-act (PDSA) cycles to implement and monitor the improvements. Finally, the team applied a bundle of interventions that included the following: (a) policies and procedures for central line insertion, maintenance and removal processes standardization, (b) physicians training for line insertion by simulation, (c) an awareness campaign that included recognizing healthcare workers and enhancing patient engagement, (d) performing root cause analysis for the CLABSI events, and (e) automation of central line insertion, and (f) maintenance bundles documentation in the hospital information system. Results The CLABSI rate per 1000 patient days dropped from 1.5 per 1000 device days to 1.03 per 1000 device days. In addition, CLABSI events reduction was 24% by 2018. Then further reduction of 15% occurred by the end of 2019. Thus, the overall decrease in CLABSI events was 35% from the baseline number of events (i.e., 144 events) in 2017. Another achievement of the project is that 10 units reported zero CLABSI events in 2018 and 2019, of which four units had a high central line utilization rate, more than 40%. Conclusion The implemented interventions effectively reduced the CLABSI events in the hospital. The project team will continue implementing more interventions with monitoring, aiming to achieve zero CLABSIs over time in all the hospital units.