Healthcare-associated infections (HAIs), recognized as one of the most important indicators of healthcare service quality, are a serious problem in Türkiye and the world. Central catheter-associated bloodstream infections (CCA-BSIs) increase the cost of treatment and cause loss of life. These infections are caused by central venous catheters (CVCs), which are commonly used medical devices in intensive care units (ICUs). Infections that occur in patients with CVCs left in place for more than 48 hours are defined as CCA-BSIs. According to the National Guidelines for Vascular Access Management (2019), 85% of BSIs are caused by catheters. The Turkish Ministry of Health reported that the rate of standardized CCA-BSIs in 2021 (1.20) increased by 10.5% compared to 2020 (1.07). Evidence-based interventions that should be implemented to prevent CCA-BSIs include not inserting CVCs into the femoral vein, paying attention to aseptic technique during catheter insertion, skin preparation with chlorhexidine, routine replacement of the catheter, use of single lumen catheters, and removal of the catheter when the indication is no longer present. One of the prevention interventions is care packages. Research shows that the CVC care bundle of five evidence-based interventions reduces the incidence of CCA-BSIs. Those five interventions are good hand hygiene, skin cleansing with chlorhexidine gluconate, no catheter insertion into the femoral vein, ensuring maximum sterile barrier, and daily assessment of CVC needs. Another important point is informing healthcare professionals who care for CVCs about prevention interventions. In light of the literature, this chapter discusses the risk factors for CCA-BSIs, evidence-based prevention interventions, and the impact of the CVC care package on prevention.