Background: Hospital-acquired infection in hospitals especially in developing countries is a challenging health problem with a great burden on patients and national economy. The incidence and risk factors varies from place to another and from time to time which necessitates continuous updating to combat the problem. Objectives: A prospective cross-sectional surveillance study was done over two-year duration at Al-Ahrar hospital, Zagazig to estimate the incidence of hospital acquired infection (HAI) and highlight the risk factors associated, to determine the antibacterial susceptibility, and to generate a modified antibiotic policy against emergence of new resistant strains. Methodology: Samples were collected from different hospital wards. Isolation and identification of bacteria, antibacterial susceptibility testing was determined. Double disc synergy test and E- test ESBL were done for MIC determination. Results: The overall incidence of HAI in the hospital was 20.6%. Burn unit was the most affected (82.4%) followed by internal medicine and ICU with incidence of (57.10% and 29.40%) respectively. The most predominant organism was Pseudomonas spp. followed by E. coli and Staphylococcus aureus. Prolonged hospital stay, medical devices such as urine catheter, ventilator, CVC and some co-morbidities act as risk factors of HAI. The highest susceptibility was to imipenem, amikacin and vancomycin while all isolates were resistant to cephalosporins. All S. aureus isolates were MRSA and 18.2% were VRSA. Ten isolates (20.8%) were confirmed as ESBL by double disc synergy test and E-test ESBL. Conclusion: The relative high incidence of HAI and resistance among the studied isolates necessitates the implementation of strict infection control practice and antibiotic policies in our hospitals.