Ventricular tachyarrhythmias may occur during intravenous arsenic trioxide (As2O3). This has not happened during oral As2O3. Sixteen patients were studied by electrocardiography and 24-hour Holter monitoring at baseline, during and after oral As2O3 (As2O3-ON, As2O3-OFF). QT and corrected QT (QTc) were significantly longer during As2O3-ON than in As2O3-OFF, but QT and QTc dispersions were comparable. The patients' 24-hour heart rates were higher during As2O3-ON than in As2O3-OFF. QTc intervals at each hour were longer during As2O3-ON than in As2O3-OFF. However, QTc prolongation of more than 30 milliseconds only occurred at one time point (2 hours) after oral As2O3, resulting in QTc of more than 500 milliseconds in 3 of 16 patients, all within 4 hours of oral As2O3. Although the standard deviation of normal RR interval was lower during As2O3-ON, ratios of low frequency to high frequency power for As2O3-ON and As2O3-OFF were comparable. No ventricular proarrhythmias were observed. These observations, due to the lower peak plasma arsenic reached during oral As2O3, may explain the relative cardiac safety of oral As2O3.