Background: Of the estimated 384,000 needle-stick injuries occurring in hospitals each year, 23% occur insurgical settings. This study was conducted to assess safe injection procedures, injection practices, andcircumstances contributing to needlestick and sharps injures (NSSIs) in operating rooms.Methods: A descriptive cross sectional approach was adopted. Modified observational checklists based onWorld Health Organization (WHO) definitions were used in operating rooms (n = 34) and interview questionnairewas administered to HCWs (n = 318) at the Alexandria Main University Hospital.Results: Safe injection procedures regarding final waste disposal were sufficiently adopted, while measuresregarding disposable injection equipment, waste containers, hand hygiene, as well as injectionpractices were inadequately carried out. Lack of job aid posters that promote safe injection and safe disposalof injection equipment (100%), overflowing of sharps containers and presence of infectious wasteoutside containers (50%), HCWs not cleaning their hands with soap and water or alcohol-based handrub (58.1%), and HCWs not wearing gloves during IV cannula insertion (58.1%), were all findings duringobservations. High prevalence of NSSIs was reported (61.3%), mostly during handling suture needles(50.8%). In addition, 66.2% of the injured HCWs were the original user of the sharp item which was contaminatedin 80% of injuries. At time of NSSI, 79% HCWs were wearing gloves. The most common injuredsites were left fingers (39.5%), and 55.4% of injuries were superficial. After exposure, 97.9% did not reporttheir exposure. The source patient was not tested for HBV, HCV and HIV infection in more than 70% ofinjuries and 96.9% of injured HCWs did not receive post exposure prophylaxis.Conclusion: The study highlighted that inadequately adopted safe injection procedures and insufficientinjection practices lead to high prevalence of NSSIs in operating rooms.