Background: This study aimed to evaluate the population pharmacokinetics of digoxin in Japanese patients and establish a dosage regimen based on the pharmacokinetic data. Methods: We analyzed 287 serum digoxin samples from 192 individuals by using the nonlinear mixed effects model. We used simulations to optimize the dosage regimen of digoxin to achieve a high likelihood of the target concentration (0.5-0.8 ng/mL). Results: The total body clearance (CL/F ([L/h]) was calculated using the following formula: CL/F=(1.21ï¼�0.0532 × CLcr [(mL/min]) × (1+0.787 × AMD), where CLcr is the creatinine clearance and AMD is 0 in the case of concomitant administration of amiodarone and 1 otherwise. To achieve the target concentration (0.5–0.8 ng/mL), the dosage of digoxin was 0.0625 mg/day (CLcr <35 mL/min and AMD=0); 0.125 mg/day (CLcr, 35–65 mL/min and AMD=0); 0.1875 mg/day (CLcr, 65–100 mL/min and AMD=0); 0.0625 mg/every other day (CLcr <30 mL/min and AMD=1); and 0.0625 mg/day (CLcr, 30–85 mL/min and AMD=1). Conclusion: Our findings suggest that population parameters are useful for evaluating digoxin pharmacokinetics.