The purpose of this study was to evaluate if dosing fentanyl, dexmedetomidine, and propofol based on ideal or adjusted vs actual weight in patients would decrease overall opioid and sedative use. This was a retrospective chart review comparing adjusted vs actual weight-based dosing protocol of mechanically ventilated (MV) intensive care unit (ICU) adult patients who required fentanyl and either propofol or dexmedetomidine. A total of 261 patients were included in which 101 patients were in the actual weight group and 160 patients were in the adjusted weight group. Total doses per MV day of fentanyl was 1042 ± 1060 µg in the actual weight group vs 901 ± 1025 µg in the adjusted weight group ( = .13). Total doses per MV day of midazolam was 20 ± 19 mg in the actual group vs 15 ± 19 mg adjusted group ( = .02). Average MV days was 8.2 vs 7.1 days, ICU length of stay was 10.6 vs 9.4 days, and self-extubation rates were 17.8% vs 4.4% in the actual group and adjusted group, respectively. Total midazolam doses per MV day were lower in the adjusted group. No significant change was seen in MV days, ICU length of stay, or self-extubation rates.