Abstract Study Objective Despite the growing popularity of intraosseous infusion for adults in emergency medicine, to date there has been little research on the pharmacokinetics of intraosseously administered medications in humans. The objective of the study was to compare the pharmacokinetics of intraosseous vs intravenous administration of morphine sulfate in adults. Methods The study followed a prospective, randomized, crossover design. Each subject was equipped with an indwelling intraosseous access device and an intravenous line. Subjects were randomized to receive a 5-mg bolus of morphine sulfate infused intraosseously or intravenously, followed by the alternate administration route 24 hours later. Serial venous blood samples (5 mL) were taken at baseline and at 13 time points over 8 hours postinfusion. Blood samples were analyzed for morphine concentration by radioimmunoassay. Pharmacokinetic parameters were calculated from the data, including maximum plasma concentration ( Cmax ), time to maximum concentration ( Tmax ), and area under plasma concentration-time curve (AUC), among others. Data were analyzed by analysis of variance. Results No statistically significant differences were observed between intraosseous and intravenous administration of morphine sulfate for nearly all of the pharmacokinetic parameters including Cmax (235 ± 107 vs 289 ± 197 ng/mL, mean ± SD, IO vs IV, respectively), Tmax (1.3 ± 0.5 vs 1.4 ± 0.5 minutes), and AUC(0-∞) (4372 ± 1785 vs 4410 ± 1930 ng min−1 mL−1 ). There was, however, a statistically significant difference in the volume of distribution in the central compartment, Vd ( P = .0247), which in the opinion of the investigators was thought to be due to a minor deposition effect near the intraosseous port or in the bone marrow. Conclusion The results support the bioequivalence of intraosseous and intravenous administration of morphine sulfate in adults.