Health-care workers are an important vaccination target group, they are more frequently exposed to infectious diseases and can contribute to nosocomial infections. We established a country-wide online monitoring system to estimate influenza vaccine uptake and its determinants among German hospital staff (OKaPII). The online questionnaire included items on vaccination behavior and reasons for and against influenza vaccination. After a pilot phase in 2016, a country-wide roll-out was performed in 2017. Questions on measles (2018) and hepatitis B (2019) vaccination status were added in subsequent years. In 2017, 2018 and 2019 in total 52, 125 and 171 hospitals with 5 808, 17 891 and 27 163 employees participated, respectively. Influenza vaccination coverage in season 2016/17 and 2017/18 was similar (39.5% and 39.3%) while it increased by 12% in 2018/19 (52.3%). Uptake was higher for physicians than for nurses. Self-protection was the most common reason for influenza vaccination. While physicians mainly identified constraints as reasons for being unvaccinated, nurses mainly referred to a lack of vaccine confidence. Of the hospital staff, 87.0% were vaccinated against measles, 6.3% claimed to be protected due to natural infection; 97.7% were vaccinated against hepatitis B. OKaPII shows that influenza vaccination coverage among German hospital staff is low. Occupational group-specific differences should be considered: physicians might benefit from easier access; information campaigns might increase nurses’ vaccine confidence. OKaPII serves as a platform to monitor the uptake of influenza and other vaccines; it also contributes to a better understanding of vaccination behavior and planning of targeted interventions.