Background: The safety and efficacy of short daily hemodialysis has been reported in the USA and Europe, but there is no report on its efficacy in Japanese patients undergoing hemodialysis. Methods: Twenty-three outpatients (14 men and 9 women, 55.8 ± 9.6 years old and 11.1 ± 6.6 years on dialysis) undergoing hemodialysis 3 times/week participated in this study. After 4 weeks’ baseline observation under conventional hemodialysis, they were subjected to short daily in-center hemodialysis (DHD, 6 times/week) for 12 weeks and then a 4-week follow-up observation period under conventional hemodialysis. Results: The mean pre-dialysis systolic and diastolic blood pressure significantly decreased in the DHD period. Antihypertensive drugs could be discontinued or the dose was reduced in 6 of 11 patients treated with such drugs. The hematocrit level tended to increase in the DHD period, and recombinant human erythropoietin could be discontinued or reduced in 7 of 14 patients. Localized skin rash caused by the adhesive tape and lidocaine patch at the blood access was observed in only 2 patients, but no other adverse events associated with DHD were noted. Conclusion: These results indicate that DHD is safe and more useful than conventional 3 times/week hemodialysis for Japanese patients undergoing hemodialysis.