Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients and negatively impacts patient outcomes. We explored the incidence and risk factors for new-onset AF among patients with ESRD undergoing renal replacement therapy, without a prior history of AF, retrieved from Taiwan's National Health Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one age- and gender-matched control and one similarly matched patient with chronic kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD. The study endpoint was the occurrence of new-onset AF and patients were followed an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per 1000 person-years for ESRD, CKD, and control patients, respectively. Among patients with ESRD, age, hypertension, heart failure, coronary artery disease, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease were significant risk factors for new-onset AF. Thus, patients with ESRD had a significantly higher risk of new-onset AF. The presence of multiple risk factors was associated with a higher possibility of AF occurrence.