BACKGROUND The current recommended starting dose of sotalol is 80 mg orally twice per day, followed by a judicious increase in dosage every 3 days under continuous telemetry monitoring. We hypothesized that sotalol administered at a higher starting dose (120 or 160 mg twice daily) would allow a more rapid attainment of therapeutic response with an acceptable safety and comparable efficacy profile. METHODS Two hundred nine inpatients with various atrial and ventricular dysrhythmias were begun on either a standard starting dose (80 mg b.i.d.) or an accelerated dose (120 or 160 mg b.i.d.) of sotalol. In-hospital occurrences of drug-related adverse effects (proarrhythmic and others), drug efficacy, and length of hospitalization were retrospectively compared between the two groups. RESULTS Ten patients (9.3%) in the 80 mg b.i.d. starting dose group experienced a cardiac adverse effect of sotalol as compared to 15 patients (14.9%) in the accelerated dose group (P = 0.286). The mean amount of corrected QT (QTc) prolongation over baseline was not significantly different between the two groups at hospital discharge (22.5 ms vs 21.6 ms, P = 0.898). There was a trend toward more noncardiac side effects of sotalol in the accelerated dose group: 2 (1.9%) versus 7(6.9%), P = 0.092. The average length of hospital stay was similar in the two groups (6.8 days vs 7.4 days, P = 0.558). CONCLUSION Initiating sotalol at 120-160 mg orally twice per day marginally increases the risk of cardiac and non-cardiac side effects compared to the standard starting regimen of 80 mg b.i.d. Such an accelerated dosing regimen neither shortened hospitalization nor had any effect on treatment efficacy in this retrospective analysis.