INTRODUCTION: Since the first COVID-19 messenger RNA vaccines became available globally for emergency or conditional use, post-marketing surveillance activities have been implemented for the monitoring of any adverse events that might arise in daily clinical practice and were not detected earlier during clinical trials. METHODS: Safety data concerning the BNT162b2 and the mRNA-1273 COVID-19 vaccines were collected from the Vaccine Adverse Event Reporting System (VAERS) for the period from December 2020 to October 15, 2021. In addition to a descriptive analysis of individuals who experienced an adverse event after vaccination, a case-non-case analysis was performed by using the Reporting Odds Ratio with 95 % confidence interval as statistical parameter for detecting differences in reporting rates between the two mRNA vaccines. RESULTS: At the cut-off date, a total of 758,040 reports were submitted to VAERS, of which 439,401 were related to the Pfizer-BioNTech (BNT162b2) vaccine and 318,639 to the Moderna vaccine (mRNA-1273). Most common adverse events following immunization for both mRNA vaccines were headache, fatigue, pyrexia, dizziness, nausea, pain, chills, and pain in extremity. A disproportionality was found for BNT162b2 as compared with mRNA-1273 for some events of special interest, such as myocarditis [ROR 2.00; 95 % confidence interval (CI), 1.93-2.06], Bell's palsy (1.34; 1.29-1.39), and anaphylactic shock (3.23; 2.96-3.53). CONCLUSION: Even if some rare adverse events were identified, our survey of post-marketing surveillance has provided further evidence of the favourable safety profile of mRNA vaccines.