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Background: What leads healthy people to enter in a volunteer register for clinical trials? This study aimed to investigate the relationship between the decision to volunteer in clinical trials for a COVID-19 vaccine and social capital, in a sample of healthy volunteers in Italy. Since social capital is characterized by trust, reciprocity, and social and political participation, we claim that it is key in leading individuals to actively take action to protect public health, and to take a risk for the (potential) benefit not only of themselves but for the entire community., Methods: This study was conducted through the administration of a questionnaire to healthy volunteers registered for a phase 1 clinical trial for a COVID-19 vaccine in the Unit Research Centre of ASST-Monza, in September 2020. The primary purpose of a phase 1 study is to evaluate the safety of a new drug candidate before it proceeds to further clinical studies. To approximate a case-control study, we randomly matched the 318 respondents to healthy volunteers (cases) with 318 people randomly selected by Round 9 of the European Social Survey (controls), using three variables, which we considered to be associated with the decision to volunteer: gender, age, and education level. To execute this matching procedure, we used the "ccmatch" module in STATA., Results: The findings highlight the positive impact of social capital in the choice of healthy individuals to volunteer in COVID-19 vaccine clinical trials. Controlling for possible confounding factors, some exemplary results show that people with a high level of general trust have a greater likelihood of volunteering compared to people with low trust (OR = 2.75, CI = 1.58-4.77); we also found that it is more probable that volunteers are people who have actively taken action to improve things compared with people who have not (for individuals who did three or more actions: OR = 7.54, CI = 4.10-13.86). People who reported voting (OR = 3.91, CI = 1.70-8.99) and participating in social activities more than other people of their age (OR = 2.89, CI = 1.82-4.60) showed a higher probability to volunteer., Conclusions: Together with the adoption of urgent health measures in response to COVID-19, government policymakers should also promote social capital initiatives to encourage individuals to actively engage in actions aimed at protecting collective health. Our findings make an empirical contribution to the research on vaccines and its intersection with social behaviour, and they provide useful insights for policymakers to manage current and future disease outbreaks and to enhance the enrolment in vaccine trials., (© 2022. The Author(s).)