The COVID-19 pandemic highlighted hurdles for healthcare delivery and personnel globally. Vaccination has been an important tool for preventing severe illness and death in healthcare workers (HCWs) as well as the public at large. However, vaccination has resulted in some HCWs requiring time off work post-vaccination to recover from adverse events. We aimed to understand which HCWs needed to take time off work post-vaccination, for which vaccine types and sequence, and how post-vaccination absence impacted uptake of booster doses in a cohort of 26,267 Canadian HCWs. By March 31, 2022, more than 98% had received at least two doses of the approved COVID-19 vaccines, following a two-dose mandate. We found that recent vaccination and longer intervals between doses were associated with significantly higher odds of time-loss, whereas being a medical resident and receiving the BNT162b2 vaccine were associated with lower odds. A history of lab-confirmed SARS-CoV-2 infection was associated with lower odds of receiving a booster dose compared with no documented infection, aOR 0.61 (95% CI: 0.55, 0.68). Similarly, taking sick time following the first or second dose was associated with lower odds of receiving a booster dose, aOR 0.83 (95% CI: 0.75, 0.90). As SARS-CoV-2 becomes endemic, the number and timing of additional doses for HCWs requires consideration of prevention of illness as well as service disruption from post-vaccination time-loss. Care should be taken to ensure adequate staffing if many HCWs are being vaccinated, especially for coverage for those who are more likely to need time off to recover.