A cost‐minimization analysis was performed to compare the direct costs of various neuromuscular blocking agents (NMBAs) in procedures of specific durations. Secondary objectives were to review the role of the NMBAs studied with respect to their place on our hospital formulary, and to develop a pharmacoeconomic methodology to be applied to other formulary decisions. Patients were stratified according to estimated length of surgical procedure; group 1 (55 patients) included surgeries estimated to take less than 2 hours, and group 2 (55 patients) included those estimated to be 2–4 hours long. Patients were then randomized to one of three intermediate‐acting NMBAs: atracurium, vecuronium, or rocuronium. Anesthesia records were used to obtain all anesthetic agents administered in the operating room, and drug costs were calculated from hospital drug acquisition costs as of December 1994. Postanesthesia care unit (PACU) costs were estimated from patient charges and converted to costs using our hospital's cost‐to‐charge ratio. Costs that were common to all study treatments or unrelated to the use of NMBAs were excluded from the analysis. Two time‐adjusted costs were calculated to determine the cost of neuromuscular blockade/hour and the total anesthesia drug costs/hour. In group 1 there were no statistical differences in NMBA cost/hour, anesthesia cost/hour, or PACU times or costs. In group 2, a significant difference was found in NMBA cost/case between atracurium ($54.23 ± 41.26, mean ± SD) and vecuronium ($31.95 ± 15.33, p=0.046). Atracurium was also significantly more costly than either vecuronium or rocuronium/hour ($21.95 ± 7.42 vs $14.39 ± 7.02 and $16.07 ± 8.15, respectively, p=0.011) and anesthesia cost/hour ($28.77 ± 7.43 vs $22.82 ± 7.46 and $23.32 ± 6.54, respectively, p=0.03). There were no differences in PACU times or costs. Based on these results, vecuronium or rocuronium is preferred over atracurium in procedures with an estimated duration of 2–4 hours. In the patient population evaluated, there were no significant cost differences among the three NMBAs in surgeries with an estimated duration of less than 2 hours.