Analysis of 6.8 million Lombardy residents revealed that one in four adults remained undervaccinated by mid-2022, with vaccine deficit—defined as missing recommended doses—creating a dose-dependent increase in health risks. Among adults over 60, the highest vaccine deficit carried a 63% increased mortality risk and 116% higher risk of severe COVID-19 requiring hospitalization. The protective effect was less pronounced in younger adults, while long COVID associations remained modest and variable. Beyond individual outcomes, this massive cohort study illuminates vaccination equity gaps, with undervaccination clustering among women, younger adults, non-European immigrants, and rural residents—patterns that may reflect access barriers rather than medical contraindications. The finding that simulated universal booster coverage could substantially reduce deaths and hospitalizations in older adults reinforces the ongoing importance of sustained vaccination campaigns, particularly as COVID-19 transitions to endemic circulation. However, as this preprint awaits peer review, these risk estimates may be refined through the editorial process. The dose-response relationship between vaccine deficit and adverse outcomes provides compelling population-level evidence for maintaining recommended vaccination schedules, especially in high-risk demographics where the protective benefits appear most pronounced.