Background Although moderate caffeine ingestion has not been shown to be arrhythmogenic, caffeine toxicity can cause severe cardiac arrhythmias, including atrial fibrillation and ventricular tachycardia. Atrial fibrillation and ventricular tachycardia have been associated with prolongation of P-wave and QRS complex durations on signal-averaged electrocardiograms. This study investigated acute effects of caffeine ingestion on signal-averaged P-wave and QRS complexes. Methods and Results Signal-averaged electrocardiograms were obtained from 12 normal subjects (6 men, 6 women; ages 21 to 26 years) before and after ingestion of caffeine (5 mg/kg body weight) or placebo in a randomized, double-blind, crossover fashion. Electrocardiograms for signal averaging were recorded from electrodes left in a constant location. After bandpass filtering (30 to 300 Hz) and amplification, signals were sampled over 7.2 minutes at 2000 Hz. Signal-averaged P-wave and QRS complex durations did not significantly change after placebo ingestion. After caffeine ingestion QRS duration prolonged in 9 of 11 subjects at 90 minutes (mean ± SEM = 0.8 ± 0.3 ms, P < .02) and in 8 of 9 after 3 hours (1.1 ± 0.2 ms, P < .001). No significant change in P-wave duration or heart rate was found after caffeine ingestion at any test interval. Average caffeine level in saliva 90 minutes after ingestion was 6.6 ± 1.6 (SD) μg/dL. Conclusions Although probably not arrhythmogenic in normal subjects, moderate caffeine ingestion does produce a small but statistically significant prolongation of signal-averaged QRS complexes. Further prolongation caused by excessive caffeine intake may be a factor in the genesis of arrhythmias associated with caffeine toxicity. (Am Heart J 1998;136:643-6.)