Background: The voltage-gated K ⁺ -channel K _v 11.1 has a central role in cardiac repolarization. Blockage of K _v 11.1 has been linked to severe cardiovascular side effects, such as acquired long QT syndrome (aLQTS), torsade de pointes arrhythmia and sudden cardiac death (SCD). K _v 11.1 is susceptible to unspecific drug interactions due to the presence of two aromatic amino acids residing in the inner vestibule of the pore. These aromatic residues are also present in the equine orthologue of K _v 11.1. This suggests that equine K _v 11.1 may also be prone to high-affinity block by a range of different chemical entities, which potentially could cause severe cardiac side effects and SCD in horses. Aim: To screen a series of commonly used drugs in equine medicine for interaction with K _v 11.1. Methods: High-throughput screening of selected compounds on human K _v 11.1 expressed in a mammalian cell line was performed using an automated patch clamp system, the SyncroPatch 384PE (Nanion Technologies, Munich, Germany). Results were validated on equine K _v 11.1 expressed in CHO-K1 cells by manual patch clamp. Results: Acepromazine maleat (IC ₅₀ = 0.5 μM) trimethoprim (IC ₅₀ = 100 μM), diphenhydramine hydrochloride (IC ₅₀ = 2 μM) and cyproheptadine hydrochloride (IC ₅₀ = 1.84 μM) inhibited equine K _v 11.1 current at clinically relevant drug concentrations. Conclusion: The results suggest that drug interaction with K _v 11.1 can occur in horses and that some drugs potentially may induce repolarization disorders in horses.