Objectives <p>This investigation assessed the effectiveness of cluster care measures in conjunction with blood transfusion protocols in the prevention of nosocomial infections associated with the use of three catheters in intensive care units (ICUs).</p> Design <p>Cross sectional study.</p> Methods <p>The investigation included 179 critically ill patients who were admitted between January 2022 and December 2023. The control group consisted of 79 patients, received routine ICU care, whereas research group consisted of 100 patients, provided with cluster care measures and stringent blood transfusion protocols. Clinical data were analyzed in both groups, including infection control capacity of Nurses for Preventing Catheter-Associated Infections, catheter infection rates, catheter-associated urinary tract infections and central line-associated bloodstream infections.</p> Results <p>The research group’s infection control capacity was substantially improved post-intervention, surpassing that of the control group, as evidenced by the results. It demonstrated significant decrease in the overall incidence of catheter infections, as well as superior clinical outcomes.</p> Conclusion <p>The overall efficacy of the interventions was significantly influenced by the integration of blood transfusion protocols including the use of leukoreduced blood products and meticulous monitoring of transfusion thresholds. The integration of cluster care measures and blood transfusion protocols was determined to be significantly more effective than traditional ICU care in the management of three-catheter-associated nosocomial infections in ICUs.</p> Clinical trial number <p>Not applicable.</p>