OBJECTIVES: Recent pharmacologic advances in perioperative sedation and analgesia have enabled the early extubation or "fast-tracking" of patients following cardiac surgery in the intensive care unit (ICU). The clinical and economic implications associated with these sedation/analgesia protocols in practice, however, remain unclear. We prospectively assessed the total costs of care and length of stay associated with three sedation/analgesia protocols for use in technology assessment of alternative management strategies. METHODS: A total of 113 cardiac surgery patients were randomized to receive in a double-blind manner either: propofol infusion with morphine bolus (Group P, n = 41); fentanyl infusion with midazolam (Group F, n = 34); or combined propofol and fentanyl infusion (Group PF, n = 38) for sedation and analgesia during intubation. We tracked resource utilization in administrative data to estimate ICU-related pharmacy costs, physician costs, hospital costs, total direct medical costs, and length of stay. Standardized, nationally representative cost estimates were used to value resource utilization in 2002 constant dollars. We used analysis of variance methods (ANOVA) to determine whether observed economic outcomes differed between sedation protocols. RESULTS: Mean observed ICU-related length of stay (days) was similar overall between groups (Group P: 1.14; Group F: 1.10; Group PF: 1.26; p = 0.630) as were average total medical costs ($21,338 vs. $20,208 vs. $20,148, respectively; p = 0.466). Mean pharmacy, physician, and hospital costs also did not significantly differ between groups (pharmacy costs: $1304 vs. $1302 vs. $1280, respectively; p = 0.976). Pair-wise comparisons between sedation approaches also did not reveal any significant difference in economic outcomes between management protocols. CONCLUSIONS: There is no evidence of significantly reduced length of stay or total costs associated with propofol-based sedation/analgesia protocols in practice. Additional research is warranted to assess clinical outcomes associated with these agents to guide clinical practice decision-making.