Objectives. This study aimed to assess the level of awareness, prevalence and risk factors of needle-stick and sharps injuries (NSSIs) in Tanta University Hospitals, Egypt to develop a well-established preventive strategy. Methods. A total of 662 healthcare workers (HCWs), including nurses and physicians, who attended work during the last 6 months of 2019 were included. Data were collected on a structured questionnaire distributed during their working time. Results. Of 662 participating HCWs, 486 were nurses and 176 were physicians. Good awareness (86.1 and 83.1%) of the participants about safe injection policy and sharp disposal after use was observed. Nurses showed a significantly higher percentage of poor awareness score (79.1%) than physicians (20.9%). NSSIs in our hospitals reached 60.4%. Nurses (67.9%) had higher risk of NSSIs than physicians (39.8%; p < 0.001). NSSIs were significantly less likely to occur for HCWs who were aware of safe injection and sharp disposal policies. NSSIs were frequent with specimen collection (16.4%), injections (15.5%) and sharp disposal (14.6%). Only 110 (27.5%) have reported their injuries. Conclusion. A comprehensive program that addresses institutional, behavioral and device-related factors that contribute to the occurrence of NSSIs and reporting systems is needed.