Knots are the weakest link in surgical sutures, serving as mechanical ligatures between filaments. Exceeding their safe operational limits can cause fatal complications. The empirical nature of present guidelines calls for a predictive understanding of the mechanisms underlying knot strength. We identify the primary ingredients dictating the mechanics of surgical sliding knots, highlighting the previously overlooked but critical effect of plasticity and its interplay with friction. The characterization of surgeon-tied knots reveals the relevant ranges of tightness and geometric features. Using model experiments coupled with finite element simulations, we uncover a robust master curve for the target knot strength versus the tying pre-tension, number of throws, and frictional properties. These findings could find applications in the training of surgeons and robotic-assisted surgical devices.