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Abstract Kjellstrand et al. (2022),https://10.1029/2021JD036232describes the evolution and dynamics of a strong, large‐scale Kelvin‐Helmholtz instability (KHI) event observed in polar mesospheric clouds (PMCs) on 12 July 2018 by high‐resolution imagers aboard the PMC Turbulence (PMC Turbo) stratospheric long‐duration balloon experiment. The imaging provides evidence of KH billow interactions and instabilities that are strongly influenced by gravity waves at larger scales. Specific features include initially separated regions of KHI, secondary convective and KH instabilities of individual billows, and “tubes” and “knots” that arise where billow cores are mis‐aligned or discontinuous along their axes. This study describes a direct numerical simulation of KH billow interactions in a periodic domain seeded with random initial noise that enables excitation of multiple KH billows exhibiting variable phase structures that capture multiple features of the observed KHI dynamics. Variable KH billow phases along their axes yield initial vortex tubes having diagonal alignments that link adjacent, but mis‐aligned, billow cores. Weak initial vortex tubes and billow cores having nearly orthogonal alignments amplify, interact strongly, and drive intense vortex knots at these sites. These vortex tube and knot (T&K) dynamics excite “twist waves” that unravel the initial vortex tubes, and drive increasingly strong vortex interactions and a cascade of energy and enstrophy to successively smaller scales in the turbulence inertial range. The implications of T&K dynamics are much more rapid and intense breakdown and decay of the KH billows, and significantly enhanced energy dissipation rates, where these interactions occur.