Ibogaine is a psychoactive indole alkaloid. Its use as anti-addictive agent was accompanied by QT prolongation and cardiac arrhythmias, which are most likely caused by hERG potassium channel inhibition. Therefore, the interaction of ibogaine with hERG channels heterologously expressed in tsA-201 cells was studied in detail. Currents through hERG channels were blocked regardless whether ibogaine was applied via the extra- or intracellular solution. The extent of inhibition was determined by the relative pH values. Block occurred during the activation of the channels and was not observed for resting channels. With increasing depolarizations ibogaine block grew and developed faster. Steady-state activation and inactivation of the channel were shifted to more negative potentials. Deactivation was slowed, while inactivation was accelerated. Mutations in the binding site reported for other hERG channel blockers (Y652A and F656A) reduced the potency of ibogaine, whereas an inactivation-deficient double mutant (G628C/S631C) was as sensitive as wild-type channels. Molecular drug docking indicated binding within the inner cavity of the channel independently of the protonation of ibogaine. Experimental current traces were fit to a kinetic model of hERG channel gating, revealing preferential binding of ibogaine to the open and inactivated state. Taken together, ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time.