BACKGROUND: The full spectrum of side effects from COVID-19 vaccinations and infections, including milder symptoms or health effects that do not lead to health care visits, remains unknown. Person-centered self-reporting of symptoms may offer a solution. Monitoring patient-reported outcomes over time will vary in importance for different patients. Individuals have unique needs and preferences, in terms of both communication methods and how the collected information is used to support care. OBJECTIVE: This study aims to describe how Symptoms, a system for person-centered self-reporting of symptoms and health-related quality of life, was utilized in investigating COVID-19 vaccine side effects. We illustrate this by presenting data from the Symptoms system in newly vaccinated individuals from the RECOVAC (Register-based large-scale national population study to monitor COVID-19 vaccination effectiveness and safety) study. METHODS: During the COVID-19 pandemic, newly vaccinated individuals were identified as the ideal population to query for milder symptoms related to COVID-19 vaccinations and infections. To this end, we used posters in observation areas at 150 vaccination sites across the Västra Götaland region of Sweden, inviting newly vaccinated individuals to use a novel digital system, Symptoms. In the Symptoms system, users can track their symptoms, functioning, and quality of life as often as they wish, using evidence-based patient-reported outcome measures and short numeric rating scales. These scales cover a prespecified list of symptoms based on common COVID-19 symptoms and previously reported vaccine side effects. Participants could also use numeric rating scales for self-defined symptoms if their symptom was not included on the prespecified list. RESULTS: A total of 731 people created user accounts and consented to share data for research between July 21, 2021, and September 27, 2022. The majority of users were female (444/731, 60.7%), with a median age of 38 (IQR 30-47) years. Most participants (498/702, 70.9%) did not report any of the comorbidities included in the questionnaire. Of the 731 participants, 563 (77.0%) reported experiencing 1 or more symptoms. The most common symptom was pain at the injection site (486/563, 86.3%), followed by fatigue (181/563, 32.1%) and headache (169/563, 30.0%). In total, 143 unique symptoms were reported. Of these, 29 were from the prespecified list, while the remaining 114 (79.7%) were self-defined entries in the symptom field. This suggests that the flexibility of the self-directed system-allowing individuals to decide which symptoms they consider worth tracking-may be an important feature. CONCLUSIONS: Self-reported symptoms in the Symptoms system appeared to align with previously observed post-COVID-19 vaccination symptoms. The system was relatively easy to use and successfully captured broad, longitudinal data. Its person-centered and self-directed design seemed crucial in capturing the full burden of symptoms experienced by users.