To determine whether concomitant use of ceftriaxone and oral or intravenous lansoprazole increases the risk of ventricular arrhythmia and cardiac arrest in the real-world setting in Japan. The data analyzed were obtained from the JMDC hospital-based administrative claims database for the period April 2014 to August 2022. Patients who received a proton pump inhibitor (PPI) while receiving ceftriaxone or sulbactam/ampicillin were identified. The frequency of ventricular arrhythmia and cardiac arrest was analyzed according to whether oral or intravenous PPI was concomitant with ceftriaxone or sulbactam/ampicillin. Estimates of the incidence of ventricular arrhythmia and cardiac arrest were then compared among the groups, using the Fine-Gray competing risk regression model. The results showed that the risk of ventricular arrhythmia and cardiac arrest was significantly higher with concomitant ceftriaxone and oral lansoprazole (hazard ratio 2.92, 95% confidence interval 1.99-4.29, P<0.01) or intravenous lansoprazole (hazard ratio 4.57, 95% confidence interval 1.24-16.80, P=0.02) than with concomitant sulbactam/ampicillin and oral or intravenous lansoprazole. Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone.