Objective: The study aimed to measure the incidence, risk factors and most frequent causative organisms of central line-associated bloodstream infections (CLA-BSI) in the Medical/Coronary and Surgical Intensive Care Units (ICUs) at a private hospital. Methods: This prospective study included 499 patients and was conducted between April 2014 and September 2014 in the Medical/Coronary ICU and Surgical ICU of a private hospital in Cairo, Egypt. Results: Approximately 44% of all the patients admitted to the ICUs underwent Central Venous Catheter (CVC) insertion. The overall incidence density rate of CLA-BSI was 6 cases per 1000 central line-days. The central line utilization rate was 0.94 per 1000 patient-days. The mortality rate among cases with CLA-BSI was 16.8% (95% CI: 13.6% – 20.4%) during the study period. Risk factors for CLA-BSI were detected by univariate analysis and included associated co-morbidities such as heart failure, APACHE II scores of >15, an ICU stay of 5 days or more, duration of CVC placement, subclavian insertion of CVCs, and mechanical ventilation. Additionally, logistic regression analysis identified a long ICU stay of 5 days or more, mechanical ventilation and the presence of heart failure as the only significant predictors. Gram-negative bacteria, especially Enterobacter (36.8%: 95% CI: 16.3%– 61.6%), Pseudomonas aeruginosa (21.1%: 95% CI: 16.0% - 45.5%) were the predominant organisms detected in CLA-BSI cases. Conclusion: CLA-BSI is an important cause of mortality in ICU patients. The infection rate is considerably higher than that in recent studies from developed counties, but it is still lower than the rates reported in comparable published studies in Egypt. Strict adherence to the standard infection prevention practices for critically ill patients is highly recommended.