Tetrodotoxin blocks voltage-gated sodium channels, which are responsible for the initiation and propagation of action potentials. Impairment of action potential conduction in myocardial cells affects the cardiac conduction system and can influence electrocardiogram output. In this retrospective study, we investigated whether tetrodotoxin poisoning prolong the PR, QRS and QTc intervals, which might be used as prognostic indices of respiratory failure after tetrodotoxin poisoning. Additionally, we evaluated whether these changes correlate with tetrodotoxin concentration in the body. Eighty-four patients were divided into two groups according to the development of tetrodotoxin poisoning-related respiratory failure requiring mechanical ventilation after pufferfish ingestion. The incidence of respiratory failure was 17.9%. There was no difference in the delay between pufferfish ingestion and the onset of symptoms between the two groups. The most common electrocardiogram abnormality was QTc prolongation (23.8%), followed by PR prolongation and QRS widening. Patients with QTc prolongation had higher urinary tetrodotoxin concentrations than patients without QTc prolongation, but no differences in the plasma tetrodotoxin concentrations were observed. Two multivariate regression models indicated that the QTc interval and QTc prolongation at presentation were independent factors for the development of respiratory failure after tetrodotoxin poisoning. Tetrodotoxin poisoning can cause electrocardiogram changes indicative of changes in the cardiac conduction system. In particular, QTc prolongation was associated with the development of respiratory failure and was correlated with the urinary tetrodotoxin concentration. It is recommended that patients poisoned with tetrodotoxin who exhibit QTc prolongation undergo regular and frequent assessments of their respiration status to prevent sudden respiratory arrest.