The coronavirus disease 2019 pandemic has imposed unprecedented occupational challenges for healthcare professionals. In dentistry, handheld instruments such as air and electric handpieces, ultrasonic scalers, and air/water syringes are capable of generating aerosols, droplets, and splatter, thereby exposing dental professionals to airborne contaminants such as viruses, bacteria, and fungi. The objective of the present study was to determine the spatial distribution of aerosols by size (0.30 to 20.00 μm) and the efficacy of a novel aerosol containment device (ACD) in a large operatory room with 12 dental chairs. Real-time portable laser aerosol spectrometers were used to measure the size-resolved number concentration of aerosols generated by a collision nebulizer. Results reported demonstrate that aerosol number concentrations significantly decreased as a function of distance with or without the utilization of the ACD. The ACD was able to efficiently decrease (up to 8.56-fold) the number and size distribution of particles in a large dental clinic. The novel device demonstrated higher efficiency for particles shown to contain the highest levels of severe acute respiratory syndrome coronavirus 2 in Chinese hospitals, thereby showing great promise to potentially decrease the spreading of nosocomial pathogens in dental settings.