Needle-stick or sharp injuries (NSIs) are critical occupational hazards for healthcare workers. Exposure to blood and body fluids through NSIs increases the risk of transmission of blood-borne pathogens among them. The objectives of this study were to estimate the annual incidence of NSIs and investigate the associated factors of NSIs among the healthcare workers in Saudi Arabia. A cross-sectional online survey was conducted between October and November 2021. A total of 361 healthcare workers participated in the survey from all over Saudi Arabia. The one-year incidence of at least one event of NSIs among the healthcare workers is estimated at 22.2% (95% CI: 18.0, 26.8). More than half of the injury events (53.8%) were not reported to the authority by the healthcare workers. Incidence of NSIs was highest among the physicians (36%) and was followed by nurses (34.8%), dentists (29.2%), and medical technologists (21.1%). The odds of NSIs was higher among the healthcare workers aged 26–30 years compared to the 20–25 years age group (OR: 2.51; 95% CI: 1.04, 6.03), as well as among the workers who directly dealt with needles or other sharp objects while working compared to those who did not (OR: 5.9; 95% CI: 2.69, 12.97). The high incidence and low rate of reporting of NSIs highlights the need of education and awareness raising programs targeting healthcare providers with higher risk of injury.