Although vaccination is one of the most cost-effective ways of preventing disease, vaccine hesitancy has been included among the ten threats of global health. Addressing low adult vaccination rates requires an adequate understanding of people’s views. We explored perceived barriers to immunization among under-vaccinated adults to identify potential differences among vaccine supporters, refuters, and those who are undecided. We conducted a multi-center, mixed-methods study at 23 primary care practices in Greece. Each day, we asked three new randomly-selected adult healthcare users who attended the practice over the course of 30 consecutive working days. We used thematic content analysis to analyze their written answers to open-ended questions that addressed reasons for not getting vaccinated. Out of 1571 participants, two-thirds reported they were under-vaccinated as adults, thus accounting for three out of five of the supporters and the vast majority of the undecided and refuters. “Concerns/fears,” a “perception of low susceptibility to disease due to good health status,” the “absence of healthcare professional’s recommendation,” and “previous negative experiences” were four themes common to all three groups. Additional barriers reported by supporters and the undecided included “knowledge gaps about the necessity of adult vaccination,” “negligence,” and lack of “accessibility.” Among refuters, additional themes identified were “mistrust in pharmaceutical companies” and “disbelief in vaccine effectiveness.” In conclusion, under-vaccination is common, not only among refuters or the undecided, but also among supporters of adult vaccination. We found similarities and differences in under-vaccinated adults’ perceived barriers, depending on their individual perspectives. Physicians and public health services should take into consideration the impact of the wide range of attitudes and beliefs in their effort to address the underlying barriers to vaccination compliance as they attempt to increase vaccination coverage in adults.