COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8(+) T cells using MHC class I (MHC-I) multimers and correlations between early differen-tiation and the durability of CD8(+) T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer(+) cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%-65.6% (23.0% on average) of the peak. MHC-I multimer(+) cells dominantly exhibit phenotypes of activated effector cells 1-2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (TSCM) cells. Importantly, the frequency of T-SCM cells 1-2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8(+) T cells, indicating that early generation of TSCM cells determines the longevity of vac-cine-induced memory CD8(+) T cell responses.