We attempted to determine the accuracy of manually splitting hydrochlorothiazide tablets. Ninety-four healthy volunteers each split ten 25-mg hydrochlorothiazide tablets, which were then weighed using an analytical balance. Demographics, grip and pinch strength, digit circumference, and tablet-splitting experience were documented. Subjects were also surveyed regarding their willingness to pay a premium for commercially available, lower-dose tablets. Of 1752 manually split tablet portions, 41.3% deviated from ideal weight by more than 10% and 12.4% deviated by more than 20%. Gender, age, education, and tablet-splitting experience were not predictive of variability. Most subjects (96.8%) stated a preference for commercially produced, lower-dose tablets, and 77.2% were willing to pay more for them. For drugs with steep dose-response curves or narrow therapeutic windows, the differences we recorded could be clinically relevant.