Background: Critically ill individuals hospitalized to intensive care units require the use of central venous catheters (CVCs), which are crucial medical devices. Objective: To investigate multiple aspects of blood stream infection in ICU patients with central venous catheters. Subjects and methods; This was an observational study on 208 patients admitted to ICU and prepared to CVC insertion with the use of central line bundle and the length of stay was ≥ 72 h. Patients were followed up for any signs of infection. If systemic catheter related infection with or without local infection was suspected, microbiological evaluation was done on monitoring signs of infection. Result: We found a statistically significant relation between catheter-related bloodstream infections (CRBSIs) incidence and comorbidities, total parenteral nutrition (TPN) use, number of CVCs, and longer CVC duration. CRBSI incidence was also significantly related to increased blood transfusion and mechanical ventilation duration. There was a significant relation between CRBSI incidence and outcome, with lower survival in CRBSI patients; 73 patients (61.3%) than non-CRBSI patients; 81 patients (91%). A significant association between development of CRBSI and prolonged ICU and hospital lengths of stay was noticed. Catheter site and ultrasound guidance were not significantly related to CRBSI risk. Conclusion: our study indicated a high incidence of CRBSIs in the ICU setting, with 57.2% of patients developing CRBSI. The study identified several risk factors associated with CRBSI, including TPN, the number of CVCs, CVC duration, blood transfusion, and duration of mechanical ventilation.