BACKGROUND: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. METHODS: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. RESULTS: The AUC₀₋₁₀ hr and C(max) values increased nonlinearly between 100 mg and 1500 mg. The slope of the AUC₀₋₁₀ hr vs dose, as well as the C(max) vs dose, plots are steepest at the lowest thiamine doses. CONCLUSION: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00981877.