Objectives The COVID-19 pandemic and the disproportional spread of the disease among otorhinolaryngologists raised concerns regarding the safety of health care staff. Therefore, a quantitative risk assessment for otologic surgery would be desirable. This study aims to quantitatively compare the risk of perioperative droplet formation between microscopic and endoscopic approaches. Study Design Experimental research. Setting Temporal bone laboratory. Methods The middle ear of whole head specimens was injected with fluorescein (0.2 mg/10 mL) before endoscopic and microscopic epitympanectomy and mastoidectomy. Fluorescent droplet deposition on the surgical table was recorded under ultraviolet light, quantified, and compared among the interventions. Drilling time, droplet proportion, fluorescein intensity, and droplet size were assessed for every procedure. Results A total of 12 procedures were performed: 4 endoscopic epitympanectomies, 4 microscopic epitympanectomies, and 4 mastoidectomies. The mean (SD) proportion of fluorescein droplets was 0.14‰ (0.10‰) for endoscopic epitympanectomy and 0.64‰ (0.31‰) for microscopic epitympanectomy. During mastoidectomy, the deposition of droplets was 8.77‰ (6.71‰). Statistical comparison based on a mixed effects model revealed a significant increase (0.50‰) in droplet deposition during microscopic epitympanectomy as compared with endoscopic epitympanectomy (95% CI, 0.16‰ to 0.84‰). Conclusions There is considerable droplet generation during otologic surgery, and this represents a risk for the spread of airborne infectious diseases. The endoscopic technique offers the lowest risk of droplet formation as compared with microscopic approaches, with a significant 4.5-fold reduction of droplets between endoscopic and microscopic epitympanectomy and a 62-fold reduction between endoscopic epitympanectomy and cortical mastoidectomy.