BackgroundVaccine confidence and coverage decreased following a death temporally but not causally related to measles vaccination in Ukraine in 2008. Large measles outbreaks including international exportations followed. Herein we characterize this experience including associated costs. MethodsMixed-methods were used to characterize this vaccine safety incident and quantify health and economic costs. Qualitative interviews illuminate the incident, social climate, and corruption that influenced vaccine confidence in Ukraine. A literature review explored attitudes toward vaccines in the USSR and post-independence Ukraine. Infectious disease incidence was examined before and after the vaccine safety incident. An economic analysis estimated associated healthcare costs, including prevention and outbreak control measures, additional vaccination activities due to failure of the 2008 campaign, treatment costs for new cases domestically and foreign exportation, and productivity loss from treatment time and mortality for new cases. FindingsVaccine hesitancy and distrust in government and public health programs due to corruption existed in Ukraine before the vaccine safety incident. The mishandling of the 2008 incident catalyzed the decline of vaccine confidence and prompted poor procurement decisions, leading to a drop in infant vaccination coverage, increased domestic measles cases, and exportation of measles. The estimated cost of this incident was approximately $140 million from 2008 to 2018. InterpretationAbsent a rapid and credible vaccine safety response, a coincidental death following immunization resulted in major outbreaks of measles with substantial economic costs. Adequate investments in a post-licensure safety system may help avoid similar future incidents.