The COVID-19 pandemic has required novel solutions, including heat disinfection of personal protective equipment (PPE) for potential reuse to ensure availability for healthcare and other frontline workers. Understanding the efficacy of such methods on pathogens other than SARS-CoV-2 that may be present on PPE in healthcare settings is key to worker safety, as some pathogenic bacteria are more heat resistant than SARS-CoV-2. We assessed the efficacy of dry heat treatment against Clostridioides difficile spores and Mycobacterium tuberculosis (M. tb) on filtering facepiece respirator (FFR) coupons in two inoculums. Soil load (mimicking respiratory secretions) and deionized water was used for C. difficile, whereas, soil load and PBS and Tween mixture was used for M. tb. Dry heat treatment at 85 °C for 240 min resulted in a reduction equivalent to 6.0-log₁₀ CFU and 7.3-log₁₀ CFU in C. difficile spores inoculated in soil load and deionized water, respectively. Conversely, treatment at 75 °C for 240 min led to 4.6-log₁₀ CFU reductions in both soil load and deionized water. C. difficile inactivation was higher by >1.5-log₁₀ CFU in deionized water as compared to soil load (p < 0.0001), indicating the latter has a protective effect on bacterial spore inactivation at 85 °C. For M. tb, heat treatment at 75 °C for 90 min and 85 °C for 30 min led to 8-log₁₀ reduction with or without soil load. Heat treatment near the estimated maximal operating temperatures of FFR materials (which would readily eliminate SARS-CoV-2) did not achieve complete inactivation of C. difficile spores but was successful against M. tb. The clinical relevance of surviving C. difficile spores when subjected to heat treatment remains unclear. Given this, any disinfection method of PPE for potential reuse must ensure the discarding of any PPE, potentially contaminated with C. difficile spores, to ensure the safety of healthcare workers.