BackgroundVaccination of older adolescents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the spring of 2021 and continued with younger adolescents throughout the summer and fall. We assessed risks of adverse events following immunization (AEFI) in adolescents aged 12–19 years following SARS-CoV-2 vaccination with a messenger RNA (mRNA) vaccine in Norway.Materials and MethodsThe study sample included 496,432 adolescents born in 2002–2009, residing in Norway, and unvaccinated against SARS-CoV-2 at the beginning of the age-specific waves of vaccination in 2021. The exposures under study were first- and second-dose SARS-CoV-2 mRNA vaccinations vs. no dose. We applied Poisson regression and self-controlled case series (SCCS) analysis to estimate incidence rate ratios (IRRs) of 17 preselected outcomes, with associated 95% confidence intervals (CIs), between vaccinated and unvaccinated subjects using predefined post-vaccination risk windows.ResultsMost outcome-specific numbers of cases were low. There were no statistically significant associations between first-dose vaccination and any of the outcomes. In the main Poisson regression, second-dose vaccination was associated with increased risks of anaphylactic reaction (adjusted IRR [aIRR]: 10.05; 95% CI: 1.22–82.74), lymphadenopathy (aIRR: 2.33; 95% CI: 1.46–3.72), and myocarditis and pericarditis (aIRR: 5.27; 95% CI: 1.98–14.05). We also observed increased incidence of acute appendicitis outside the 14-day risk window. When expanding the risk window to 42 days in a post-hoc analysis, there was increased incidence of acute appendicitis following both first-dose vaccination (aIRR: 1.39; 95% CI: 1.09–1.78) and second-dose vaccination (aIRR: 1.43; 95% CI: 1.07–1.91). Results of the SCCS analysis were similar to the Poisson regression.ConclusionsIn general, potential AEFI were rare among adolescents. We found increased risks of anaphylactic reaction, lymphadenopathy, and myocarditis and pericarditis following second-dose vaccination. There were also indications of increased acute appendicitis risk when applying longer risk windows.