There are concerns regarding the side effects of the new coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine among healthcare workers (HCWs) in the United States. The objective of the study was to investigate the side effects of the mRNA-1273 vaccine with detailed review of organ systems. A randomized, cross-sectional study using an independent online survey questionnaire was conducted to collect responses from HCWs. Of all participants, 87.8% (1116/1271) provided complete responses. Of them, 38.7% (432/1116) received the mRNA-1273 vaccine, among which, 89.35% were females; 425 of these 432 mRNA-1273 vaccine recipients (98.34%) reported at least one or more symptoms. The results were classified based on the frequency of symptoms reported postvaccination. Of these, 254/432 (58.8%)were able to continue their daily routine activities. 108/432 (25%) temporarily had trouble to perform daily activities, 120/432 (27.78%) required transient time off from work, 17/432 (3.94%) required help from an outpatient provider, 1/432 (0.23%) required help from emergency department, and none of them were hospitalized. Despite the wide array of self-reported symptoms, 97.02% of the HCWs did not intend to skip the second dose of vaccine. Among all the symptoms reported, localized pain, generalized weakness, headache, myalgia, chills, fever, nausea, joint pains, sweating, localized swelling at the injection site, dizziness, itching, rash, decreased appetite, muscle spasm, decreased sleep quality, and brain fogging were the most commonly reported symptoms (in descending order of occurrence). Most of the symptoms reported were nonlife threatening. Despite the wide array of selfreported symptoms, there appears to be a higher acceptance for this vaccine.