Introduction: Parasympathetic dysfunction may play a role in the genesis of arrhyth-mias in Chagas disease. Aim: This study evaluates the acute effects of pyridostigmine (PYR), a reversible cholinest-erase inhibitor, on the occurrence of arrhythmias in patients with Chagas cardiac disease. Method: Following a double-blind, randomized, placebo- controlled, cross- over proto-col, 17 patients (age 50±2 years) with Chagas cardiac disease type B underwent 24- hour Holter recordings after oral administration of either pyridostigmine bromide (45 mg, 3 times/day) or placebo (PLA).Results: Pyridostigmine reduced the 24- hours incidence (median [25%- 75%]) of pre-mature ventricular beats—PLA: 2998 (1920- 4870), PYR: 2359 (940- 3253), P=.044; ventricular couplets—PLA: 84 (15- 159), PYR: 33 (6- 94), P=.046. Although the total number of nonsustained ventricular tachycardia in the entire group was not different (P=.19) between PLA (1 [0- 8]) and PYR (0 [0- 4]), there were fewer episodes under PYR in 72% of the patients presenting this type of arrhythmia (P=.033). Conclusion: Acute administration of pyridostigmine reduced the incidence of nonsus-tained ventricular arrhythmias in patients with Chagas cardiac disease. Further studies that address the use of pyridostigmine by patients with Chagas cardiac disease under a more prolonged follow- up are warranted.