<b><i>Background:</i></b> Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. <b><i>Objective:</i></b> The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. <b><i>Methods:</i></b> We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (<i>n</i> = 40) versus lidocaine and midazolam (<i>n</i> = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients’ quality of life (QoL) as assessed by a visual analog scale (VAS). <b><i>Results:</i></b> The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. <b><i>Conclusion:</i></b> Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients’ QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

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