AbstractThere is growing concern that Coronavirus Disease 2019 (COVID-19) vaccine fatigue will be a major obstacle in maintaining immunity in the general population. In this study, we assessed vaccine acceptance in future scenarios in two conjoint experiments, investigating determinants such as new vaccines, communication, costs/incentives and legal rules. The experiments were embedded in an online survey (n = 6,357 participants) conducted in two European countries (Austria and Italy). Our results suggest that vaccination campaigns should be tailored to subgroups based on their vaccination status. Among the unvaccinated, campaign messages conveying community spirit had a positive effect (0.343, confidence interval (CI) 0.019–0.666), whereas offering positive incentives, such as a cash reward (0.722, CI 0.429–1.014) or voucher (0.670, CI 0.373–0.967), was pivotal to the decision-making of those vaccinated once or twice. Among the triple vaccinated, vaccination readiness increased when adapted vaccines were offered (0.279, CI 0.182–0.377), but costs (−0.795, CI −0.935 to −0.654) and medical dissensus (−0.161, CI −0.293 to −0.030) reduced their likelihood to get vaccinated. We conclude that failing to mobilize the triple vaccinated is likely to result in booster vaccination rates falling short of expectations. For long-term success, measures fostering institutional trust should be considered. These results provide guidance to those responsible for future COVID-19 vaccination campaigns.