Background: To overcome the shortage of blood and blood products, it is necessary to increase the total volume of blood collected from donors. This requires modifying the current standard of 200-ml whole-blood collection for young people (16-17 year-old), which is specified by the Departmental Regulation No.22 (Kouseishou-rei dai-22 gou). The objectives of this study were to evaluate the safety of 400-ml whole-blood collection in 17-year-old males. Methods: A total of 322 male volunteers aged 17 years and 363 aged 18 or 19 years were recruited for blood collection through advertisements at schools and blood center donation sites. Blood collected from the 17-year-old males was not used for transfusion, whereas that collected from the 18-19 year-olds was used for transfusion as normal. To evaluate the safety of 400-ml whole-blood collection in the 17-year-old males, Fisher's exact test was used to compare vasovagal reaction (VVR) occurrence rates between the two groups by using a two-by-two contingency table. Significance was defined as P<0.05. Results: Among the 17-year-old males, six side effects (1.86%)-five cases of VVR and one of subcutaneous hemorrhage-were observed at the blood collection site. Among the 18-19 year-olds, eight cases of VVR (2.22%) were reported. As for late-onset donor reaction, 56 (17.7%) were reported in the 17-year-old males and 35 (10.0%) in the 18-19 year-olds as assessed by post donation questionnaire. No difference was observed in the recovery rate of biochemical data (plasma components) between the two groups. Conclusion: In terms of the VVR occurrence rate, there was no significant difference between the two groups (P=0.7935; P>0.05). The recovery rate of cell counts and plasma components to the original level was similar between the two groups. We conclude that 400-ml whole-blood collection can be performed safely in 17-year-old males in Japan.