The atypical antipsychotic clozapine is a prominent treatment for refractory schizophrenia. This drug inhibits the human ether-à-go-go related gene (hERG) and prolongs the QT-interval on the electrocardiogram. Although these biomarkers are sensitive predictors of the risk of Torsade de Pointe (TdP) arrhythmia, the long standing clinical use of clozapine did not show consistent association with increased incidence of TdP. It has recently been suggested that inhibition of other ion channels influencing the ventricular action potential can contribute refine true torsadogenic risk assessment. Here we have profiled clozapine on seven such currents using an automated electrophysiology platform. CHO or HEK cells expressing the human ion channels retained by the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative were recorded in whole-cell mode at room temperature on a Qpatch 48X planar patch-clamp workstation (Sophion, Denmark). Cells were exposed to cumulative concentrations of clozapine in saline buffer containing 0.3% DMSO supplemented with 0.06% Pluronic F-68. Clozapine concentration-dependently inhibited currents through Kv11.1 (hERG), Cav1.2, Nav1.5 (peak), Kv7.1 and Kv4.3 channels with IC50‘s of 4.2 ± 0.6 µM, 11 ± 2.4, µM, 10 ± 1.8 µM, 12 ± 1.2 µM and 54 ± 5.5 µM, respectively. The late NaV1.5 current through persistently opened channels by the sea anemone toxin ATX-II was inhibited as strongly as hERG with an IC50 of 5.5 ± 0.3 µM. In contrast, outward currents through Kir2.1 channels were reduced by only 28 ± 2.5 % at 100 µM clozapine. These data suggest that simultaneous inhibition of multiple cardiac ion channels underlies the low pro-arrhythmia risk profile of clozapine, although the submicromolar therapeutic free plasma concentrations in patients should be taken into account. How this balanced ion-channel profile translates into QT prolongation deserves further studies in integrated systems.