Background: Comatose acute stroke patients are at high risk of malnutrition, especially hypoproteinemia. However, when to start and how to provide nutrition to these patients are unclear. The purpose of this study was to determine the optimum timing and methods of nutritional supplementation to comatose acute stroke patients. Methods: A total of 273 comatose acute stoke patients who were unable to eat were enrolled. They received peripheral intravenous low-calorie solutions for the first 4 days after admission (days 0-3), and serum protein concentrations were measured on days 2, 3, and 4. From day 4, 5 different nutritional regimens were administered (25 kcal/kg/day), (including enteral nutrition [EN], total parenteral nutrition [TPN], tube feeding of 20% glucose solution, and combinations of these nutritional supplementations),. Serum concentrations of total protein and albumin were measured on days 10, 14, and 21. The patients who had EN until day 21 from day 4 were defined as EN group, and who had TPN were as TPN group. Results: Serum protein concentrations decreased slightly on day 2 and decreased significantly on days 3 and 4. From day 4 to 14, the recovery of serum protein was better in the TPN group than in the EN group. Conversely, after day 14, recovery from hypoproteinemia was better in the EN group than in the TPN group. However, when diarrhea was caused by EN, further hypoproteinemia occurred and caused patients to require TPN. The recovery from hypoproteinemia was earliest in patients receiving TPN with 20% glucose fed through a nasogastric tube from day 4 to 13 followed by EN after day 14. Hospitalization was statistically shorter for patients with a nutritionally early recovery than for patients with a delayed recovery, but clinical outcome did not differ significantly between the groups. Conclusion: It is nutritionally disadvantageous not to start nutritional support within 3 days after admission in comatose acute stroke patients. However, starting EN too early is not nutritionally beneficial, and TPN with 20% glucose fed through a tube is recommended as adequate nutrition for these patients. However, TPN should not be employed for longer than 10 days, because switching to EN after this period contributes to better nutritional recovery than continuing TPN.