BACKGROUND The utility of nurse-administered propofol sedation (NAPS) compared with midazolam and meperidine (M/M) for EUS is not known. OBJECTIVE To compare recovery times, costs, safety, health personnel, and patient satisfaction of NAPS and M/M for EUS. METHODS Prospective, randomized, single-blinded trial. METHODS Tertiary-referral hospital in Indianapolis, Indiana. METHODS Outpatients referred for EUS. METHODS Sedation with M/M or NAPS. The patient and recovery nurse were blinded; however, the sedating nurse, endoscopist, and recording research nurse were unblinded to the sedatives used. A capnography, in addition to standard monitoring, was used. A questionnaire and visual analog scale assessed patient, endoscopist, and sedating nurse satisfaction. METHODS Recovery times, costs, safety, health personnel, and patient satisfaction in both groups. RESULTS Eighty consecutive patients were randomized to NAPS (n = 40) or M/M (n = 40). More patients in the propofol group were current tobacco users; patient demographics, procedures performed, mean procedure length, and the overall frequency of adverse events were otherwise similar. Compared with M/M, NAPS was associated with a faster induction of sedation (2.3 vs 5.7 minutes, respectively; P = .001) and full recovery time (29 vs 49 minutes, respectively; P = .001), higher postprocedure patient satisfaction, and quicker anticipated return to baseline function. At discharge, total costs (recovery plus medications) were similar between the propofol ($406) and M/M groups ($399; P = .79). CONCLUSIONS Low-risk patient population. CONCLUSIONS Compared with M/M, NAPS for an EUS offered a faster sedation induction and full recovery time, higher postprocedure patient satisfaction, and a quicker anticipated return to baseline function. Total costs were similar between the groups.