The cardiac toxicity of LV5FU2 (de Gramont) regimen which is a widely used chemotherapy regimen in gastrointestinal system cancers is not well defined. We aimed to evaluate the impact of this regimen on cardiac rhythm. Two Holter ECG recordings were obtained in all patients with gastrointestinal system cancers treated with LV5FU2 regimen as first-line chemotherapy (one before and the second during the first 24 h of chemotherapy). Records were reviewed for the heart rate, rhythm, atrial premature complexes (APC), ventricular premature complexes (VPC), grades according to Lown-Wolf grading system and ST segment changes. Holter ECG recordings were evaluated in 27 patients. In the baseline evaluation, neither clinical symptom nor ST segment changes were observed. During the treatment period, chest pain was observed in two patients without any cardiac enzyme and ST segment changes. Moreover, a decrease in mean heart rate, and an increase in the number and complexity of premature complexes secondary to treatment were observed. The mean heart rate, APC per hour and VPC per hour (+/-SD) before vs. during treatment were, respectively, 93.1+/-16.4 vs. 81.6+/-12.7 (p=0.001), 18.9+/-54.0 vs. 45.3+/-53.8 vs. (p=0.049) and 12.7+/-29.6 vs. 38.1+/-42.1 (p=0.002). LV5FU2 regimen leads to a decrease in mean heart rate and a significant increase in APC and VPC which may lead to serious arrhythmias. These effects must be better understood for a safer administration of this useful and widely used drug regimen.