We hypothesized that operating room (OR) airborne particulate matter (PM) was different in quantity and mutagenic potential than office air and cigarette smoke. Exposure to surgical smoke has been equated to cigarette smoking and thought to be hazardous to health care workers despite limited data. PM was measured during 15 operations in ORs with 24.8 ± 2.0 air changes/hour, and in controls (cigarettes, office air with 1.9-2.9 air changes/hour). Mutagenic potential was assessed by γH2AX staining of DNA damage in small airway epithelial cells co-cultured with PM. Average PM concentration during surgery was 0.002 ± 0.002 mg/m3 with maximum values at 1.08 ± 1.30 mg/m3. Greater PM correlated with more diathermy (ρ = 0.69, p = 0.006). Values were most often near zero, resulting in OR average values similar to office air (0.002 ± 0.001 mg/m3) (p = 0.32). Cigarette smoke average PM concentration was significantly higher, 4.8 ± 5.6 mg/m3 (p < 0.001). PM collected from 14 days of OR air caused DNA damage to 1.6 ± 2.7% of cultured cells, significantly less than that from office air (27.7 ± 11.7%, p = 0.02), and cigarette smoke (61.3 ± 14.3%, p < 0.001). The air we breathe during surgery has negligible quantities of PM and mutagenic potential, likely due to low frequency of diathermy use coupled with high airflow. This suggests that exposure to surgical smoke is associated with minimal occupational risk.