BACKGROUND: While vaccination plays a critical role in the global response to the COVID-19 pandemic, vaccine rollout remains suboptimal in Nigeria and other Low- and Middle-income countries (LMICs). This study documents the level of hesitancy among health workers (HWs) during the initial COVID-19 vaccine deployment phase in Nigeria and assesses the magnitude and determinants of hesitancy across Nigeria. METHODS: A cross sectional study across all States in Nigeria was conducted with over 10,000 HWs interviewed between March and April 2021. Data were cleaned and analyzed with proportions and confidence intervals of hesitancy documented and stratification by HW category. We compared the level of confidence/acceptance to be vaccinated across Nigeria and documented the sources of negative information amongst HWs who refused the vaccine. FINDINGS: Among the 10 184 HWs interviewed, 9 369 [92% (95% CI= 91, 92)] were confident of the COVID-19 vaccines and were already vaccinated at the time of this survey. Compared to HWs who were less than 20 years old, those aged 50 - 59 years were significantly more confident of the COVID-19 vaccines and had been vaccinated (OR=3.8, 95% CI=2.3 - 6.4, p<0.001). Only 858 (8%) of the HWs interviewed reported being hesitant with 57% (479/858) having received negative information, with the commonest source of information from social media (43.4%.). INTERPRETATION: A vast majority of HWs who were offered COVID-19 vaccines as part of the first phase of national vaccine roll out were vaccinated and reported being confident of the COVID-19 vaccines. The reported hesitancy was due mainly to safety issues, and negative information about vaccines from social media. The issues identified remain a significant risk to the success of subsequent phases of the vaccine rollout in Nigeria. FUNDING: None.