Background COVID-19 pandemic has remained one of the leading causes of death which claimed the lives of many well-trained and experienced healthcare professionals. Vaccination is the most effective way of controlling infectious diseases, while success is challenged by individuals and groups who choose to delay or refuse vaccines. The objective of the present study was to assess the intention of healthcare workers in Eastern Ethiopia to receive the second round of COVID-19 vaccine. Methods Institution-based cross-sectional survey research design was used to collect quantitative data from a representative sample of healthcare workers in Dire Dawa, Haramaya, and Harar towns of Eastern Ethiopia. The correctly filled questionnaires were selected and entered into SPSS software for further analysis, where frequency tables, percentages, mean, and multinomial logistic regression analysis were used in the process. Results The findings revealed that most (61.6%) of the research participants are willing to receive the second round of COVID-19 vaccine, and 10.3% reported that they have not decided yet. Moreover, the main reason for respondents’ lack of intention to receive the second round of COVID-19 vaccine is the belief that the first round of COVID-19 vaccine is sufficient to prevent infection (27.8%) followed by concern over the safety or side effects of the vaccine (26.6%). Above all, the healthcare workers’ intention of taking the second round of COVID-19 vaccine is significantly associated to having children (OR=0.362, P <0.05; 95% CI: 3.279–5465.189), previous interaction with someone infected by COVID-19 (OR=1.480, P <0.05; 95% CI: 3.949–0.055), the perception that COVID-19 causes a severe illness (OR=0.018, P <0.05, 95% CI: 13.489–196.391), and experience of receiving the first round of COVID-19 vaccine (OR=50431.104, P <0.01; 95% CI: 408.789–626.00). Conclusion The present study has shown that healthcare workers in Eastern Ethiopia have a good intention of receiving the second round of COVID-19 vaccine. Nevertheless, the findings have also made it clear that there are still issues to be addressed as far as both willingness to receive the second round of the vaccine and experience of taking the first round of the vaccine are concerned. It is, therefore, important that sufficient training should be given to the healthcare workers in the area in order to raise their level of awareness and enhance their willingness to receive the second round of the vaccine.

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