Background: This study provides on important analysis of blood stream infections trends in a tertiary care setting. Objective: To determine the significant causative agents of morbidity in general Inpatients and Critical Care Units (ICU & CCU) blood isolates, Makkah, Saudi Arabia, Makkah, Kingdom of Saudi Arabia. Methodology: This work was a retrospective study aiming to analyze the positive blood cultures trends from 1st January 2004 –30th November 2015 recorded in a hospital information system at the Department of Clinical Microbiology at Al Noor Specialist Hospital. Results: Over the twelve years, bacteremia due to G-ve bacteria (GNB) was found to be more prevalent than G+ve bacteria (GPB) along with a persistent increasing trend of blood stream infections (BSIs) due to Candida spp. The prevalence of bacteremia due to Gram-negative bacteria was more than the Gram-positive bacteria in general medical wards and the CCU. In the CCU, Acinetobacter spp. (16.59%), S. aureus (15.57%), and Klebsiella spp. (14.69%) were the main causes of BSIs, while S. aureus (17.32%), Streptococci spp, (11.99%), E. coli (10.42%), and Klebsiella spp. (10.19%) were the main causes of bacteremia in general medical wards. Conclusion: In comparison to previous reports, our data suggests an upsurge in risk of Gram-negative bacteremia among CCU patients. These findings are also of key significance to epidemiologists and health policy makers in order to forecast the microbial trends.