Operating rooms (ORs) often have door openings connected to uncontrolled areas that are more contaminated. Opening the door may allow an inflow of contaminated air, degrade the microbiological air cleanliness and possibly cause surgical site infections (SSIs). This study numerically investigated the transient airflow and bacteria-carrying particles spread caused by the opening of a sliding door in an OR with mixing ventilation. Results showed that a single door opening raises the overall OR contamination by 2.1 colony-forming units per cubic metre (CFU/m3) under a temperature difference of about 3°C. With a similar level of overall contamination, the risk of infections differs dramatically, as the corresponding contamination at the surgical site ranges from lower than 1 CFU/m3 to higher than 10 CFU/m3. This implies that quantifying only the air volume exchange is not sufficient for a valid and reliable assessment of the impact of door openings on the risk of SSIs. Temporarily reducing the OR exhaust flow during door operation was found to be an effective solution to minimize the impact of door openings on the risk of infections. In the case examined in the present study, a 20–30% reduction in OR exhaust flow decreases the airborne contamination to a sufficiently low level.