Introduction Many COVID-19 vaccines have been emerging with different efficacy and safety profiles. So far, very little attention has been paid to severity and reactogenicity of COVID-19 vaccine among healthcare workers. Thus, the aim of this study is to investigate the side effects associated with the first dose of AstraZeneca COVID-19 vaccine among healthcare workers (HCWs) and nonhealthcare workers (non-HCWs). Method This is an observational cross-sectional study conducted at King Abdullah bin AbdulAziz University Hospital, Saudi Arabia, between February 28 and March 12, 2021. The major outcomes were the reported side effects of day 1, day 2, and day 3 after vaccination among HCWs and non-HCWs. Other outcomes included the onset and the duration of the reactions or the side effects that were reported. Results A total of 526 participants completed the survey with 173 (32.8%) HCWs and the remaining majority were non-HCWs. Some of the most frequently reported side effects among the participants on the first day were muscle aches (49%), followed by fever (42%) and headache (40%). HCWs experienced more muscle aches, headache, sore throat, and abdominal pain, which were statically significant, compared to non-HCWs. The mean onset of symptoms was 16 (±15.3) h in the HCW arm compared with 12.2 (±10.2) h in non-HCWs ( p = 0.0024). Furthermore, the mean duration of symptoms in the HCW group was 37 (±19) h compared with 32.3 (±13) h in the non-HCW group ( p = 0.067). Conclusion The reported side effects were common but not pressing in both groups. HCW respondents appeared to have more COVID-19 vaccine-associated symptoms.

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