Background The purpose of this study was to examine the mild and moderate side‐effects experienced by the healthcare workers (HCWs) in the Eastern Province of Saudi Arabia after receiving the booster dose of the Pfizer-BioNTech/BNT162b2 COVID‐19 vaccine. Methods We directed a descriptive cross-sectional study among adults living in the Eastern Province of Saudi Arabia. A survey link was distributed through WhatsApp, SMS, or e-mail to HCWs. Participants’ general and demographic information were also collected, as well as information about any local and systemic side‐effects reported following vaccination. Results The results of this study showed that 81.84% (401/490) of the HCWs who contributed to this study reported the minimum COVID‐19 post‐vaccination side‐effect. Body pain (89%) and pain at the site of injection (88.73%) were the most frequent frequently reported side‐effects, followed by headache (28.68%), joint or bone pain (27.18%), muscle pain (26.43%), nausea or vomiting (21.2%), fever (18.95%), skin rashes (10.22%). History of chronic diseases had a 0.44‐fold increased risk of side-effects compared to no history of chronic diseases HCWs (adjusted odds ratio (aOR) = 0.44; 95% CI = 0.224, 0.880), and significant association of occupation with side-effects was also 1.61-fold increased risk compared to nonmedical ((aOR) = 1.61; 95% CI = 1.037, 2.513). Conclusion According to this study, the Pfizer-BioNTech/BNT162b2 COVID-19 vaccine was safe when given to Saudi Arabian HCWs. All reported side‐effects were mild to moderate. The outcomes indicated that most participants had body pain and pain at the site of injection and fatigue is among the least reported side-effect post-booster dose. Healthcare was highly connected with more reporting of side‐effects.