NK cells represent a critical component of the host innate immune response to viral infection and tumor transformation. Nevertheless, the fate of recently degranulated NK cells subsequent to a primary target cell interaction remains largely unexplored. Here, we investigated the long-term viability and killing potential of human NK cells following target cell lysis using live-sorting of CD107a-degranulated NK cells. We observed that sorted CD107a+ NK cells exhibited continued lytic potential against a wide variety of target cells, including tumor and virally infected target cells. CD107a-positive- and CD107a-negative-sorted NK cells displayed similar long-term viability, killing potential, and response to inflammatory cytokines such as IL-2, IL-15, and IFN-alpha. Interestingly, we observed that the CD107a signature is remarkably stable over time and that recently degranulated NK cells exhibit an amplification of CD107 expression immediately following a target cell interaction. Together, our data expand previous data showing that NK cells retain the capacity to kill multiple target cells in succession and reveal that NK viability, cytotoxicity, and response to inflammatory cytokines are not altered following a primary target cell interaction. Overall, our data argue for the strength of the NK cell compartment in the continuous surveillance of tumor and virally infected cells in the body and highlight the use of using CD107a expression as a stable marker for NK cytotoxicity.