Objective: The aim of this prospective clinical study is to evaluate the feasibility of the micro-laryngeal surgery (MLS) using a 3D operating exoscope (OE) in substitution to a conventional operating microscope (OM). Methods: A total of 41 consecutive patients were included (male: 26; median age: 55.0 years; IQR: 46.0-68.0). After each procedure, the surgeon and the scrub nurse were asked to fill out a tailored questionnaire on a 3-point Likert scale (1—not acceptable, 2—acceptable, 3—good) including 12 items. Results: The majority of the procedures were therapeutic (n = 31, 75.6%), while the remaining were diagnostic (n = 10, 24.4%). All surgeries were successfully completed without the support of the OM, and no complications or unwanted delays were detected. The majority of the individual items were judged “good” either by surgeons (n = 399, 81.1%) and scrub nurses (n = 287, 87.5%). The natural posture during the procedure, and the ease of use the joystick and focusing were the best-rated items by the surgeons. Conclusions: This study demonstrates the feasibility of MLS using the OE. Further comparative clinical studies are needed to clarify its real value in substitution to a conventional operating microscope and to better define advantages and disadvantages.