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Current practical methods for finding the equilibrium dissociation constant, K d , of protein-small molecule complexes have inherent sources of inaccuracy. Introduced here is "accurate constant via transient incomplete separation" (ACTIS), which appears to be free of inherent sources of inaccuracy. Conceptually, a short plug of the pre-equilibrated protein-small molecule mixture is pressure-propagated in a capillary, causing fast transient incomplete separation of the complex from the unbound small molecule. A superposition of signals from these two components is measured near the capillary exit and used to calculate a fraction of unbound small molecule, which, in turn, is used to calculate K d . Herein the validity of ACTIS is proven theoretically, its accuracy is verified by computer simulation, and its practical use is demonstrated. ACTIS has the potential to become a reference-standard method for determining K d  values of protein-small molecule complexes., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)