Benzodiazepines are the most commonly used sedatives for the reduction of patient anxiety. However, they have adverse intraoperative effects, especially in obstructive sleep apnea (OSA) patients. This study aimed to compare dexmedetomidine (DEX) and midazolam (MDZ) sedation considering intraoperative complications during transurethral resections of the bladder and prostate regarding the risk for OSA. This study was a blinded randomized clinical trial, which included 115 adult patients with a mean age of 65 undergoing urological procedures. Patients were divided into four groups regarding OSA risk (low to medium and high) and choice of either MDZ or DEX. The doses were titrated to reach a Ramsay sedation scale score of 4/5. The intraoperative complications were recorded. Incidence rates of desaturations (44% vs. 12.7%, p = 0.0001), snoring (76% vs. 49%, p = 0.0008), restlessness (26.7% vs. 1.8%, p = 0.0044), and coughing (42.1% vs. 14.5%, p = 0.0001) were higher in the MDZ group compared with DEX, independently of OSA risk. Having a high risk for OSA increased the incidence rates of desaturation (51.2% vs. 15.7%, p < 0.0001) and snoring (90% vs. 47.1%, p < 0.0001), regardless of the sedative choice. DEX produced fewer intraoperative complications over MDZ during sedation in both low to medium risk and high-risk OSA patients.