Introduction: The choice of anesthetic agents plays a crucial role in procedural success. This study aimed to compare the effects of propofol-fentanyl and propofol-dexmedetomidine combinations, focusing on patient and surgeon perspectives in outpatient procedures. Methods: A randomized, controlled, triple-blind clinical trial including 128 adult patients undergoing elective outpatient surgical procedures with sedation and local anesthesia. Patients were randomized to receive either propofol-fentanyl (PF, n = 64) or propofol-dexmedetomidine (PDex, n = 64). Primary outcomes were patient satisfaction, assessed using the ISAS-Br score, and the adequacy of sedation, evaluated by the surgeon and measured by a Numerical Rating Scale (NRS) for movement. Respiratory and hemodynamic changes, as well as awakening from anesthesia, adverse events during recovery, and time to hospital discharge were compared. Results: No difference between patient satisfaction scores (median ISAS-Br [IQR]: PF 2.64 [2.45‒3.00] vs. PDex 3.00 [2.45‒3.00], p = 0.252). The PF group had a significantly lower movement score (median NRS [IQR]: 0.5 [0.00‒2.25] vs. 2.0 [0.00‒5.00], p = 0.006). The incidence of intraoperative events related to respiration and hemodynamics, as postoperative pain and postoperative nausea/vomiting were similar. A higher proportion of patients sedated with PF awoke in the operating room (75% vs. 35.9%, p < 0.001), and 98.4% of the PF group vs. 92.2% of the PDex group were ready for hospital discharge in less than thirty minutes, p = 0.208. Conclusion: Single doses of fentanyl or dexmedetomidine combined with propofol resulted in equivalent patient satisfaction, safety, and discharge times. The propofol-fentanyl combination demonstrated superior sedation adequacy from the surgeon’s perspective and facilitated a faster emergence from anesthesia.