OBJECTIVES: Meperidine/midazolam (M/M) and propofol (P) are clinically effective alternatives for sedation during endoscopic procedures. Propofol has a higher acquisition cost, but may be associated with cost savings due to shorter duration of post-procedure care. The objective of this project was to compare the costs associated with complex upper endoscopic procedures (ERCP/EUS) in subjects who received either M/M or propofol. METHODS: Subjects scheduled for ERCP/EUS were randomized to receive M/M or P during the procedure. A blinded observer assessed time to recovery using a standard 10-point postanesthesia recovery score (PARS) every 15 minutes. Once a PARS score of 10 was reached, the study terminated and the subject was discharged from the recovery ward. The cost of drug (source: Redbook), an anesthetist for the propofol group (source: Bureau of Labor Statistics), recovery room personnel costs (source: Bureau of Labor Statistics), and overhead costs were compared from the institutional perspective. A sensitivity analysis was performed by assuming generic drug, a nurse anesthetist, and licensed practical nurse (LPN) care in the recovery ward. RESULTS: 33 and 31 subjects were randomized to receive M/M and P, respectively. There were no significant differences detected between the groups in age, gender, case severity, or procedure duration. P group subjects had a significantly shorter post-procedure recovery time (19 minutes) compared with M/M group subjects (71 minutes, p<0.001). Subjects in the M/M group cost an average of $65 per case, while P group subjects cost an average of $144 per case (p<0.001). The sensitivity analysis resulted in an average cost of $77 per case in the P group and $34 in the M/M group (p<0.001). CONCLUSIONS: Subjects in the P group had a significantly shorter post-procedure recovery time but this did not result in cost savings compared with subjects treated with M/M.