(1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan antistaphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poliglecaprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h.< Réduire