Autoclaving at 121°C for 15 minutes is the most reliable method for sterilizing heat-resistant surgical instruments because it uses steam under pressure to achieve complete microbial kill, including bacterial spores. The high temperature and pressure combination ensures rapid and effective sterilization, surpassing methods like boiling or chemical soaking. This method maintains instrument integrity while ensuring sterility, crucial for preventing postoperative infections. Autoclaving is the gold standard for sterilizing surgical tools due to its proven efficacy and reproducibility in clinical settings.

Reference: Medical Microbiology, Murray et al., 9th Edition.