Objective Under 2 methods of guidance: indirect energy metabolism measurement and classical Harris-Benedict (HB) formula to carry out enteral nutritional support program to observe the difference in influence on nutritional status and prognosis of the patients. Methods Sixty patients with critical coma admitted to the Department of Critical Care Medicine of the 903rd Hospital of PLA from November 2015 to April 2017 were enrolled, and they were divided into a metabolic vehicle group (30 cases) and a formula group (30 cases) according to the random number digital table. All the patients were treated with stage nutritional therapy according to the daily energy consumption, which was measured by indirect energy metabolism measurement or HB formula. The change of serum albulmin (Alb), blood hemoglobin (Hb) and peripheral blood total lymphocyte count (TLC) before treatment and after 1 week and 2 weeks of nutritional support and the incidence of complications and prognosis after 2 weeks of nutritional support were observed; the difference of mid-upper arm circumference (MAC) was compared between before nutritional support. Results After the nutrritional therapy, serum Alb, Hb, and TLC in two groups were obviously higher than those before treatment, the degrees of elevation in metabolic group were more significant than those in the formula group [Alb (g/L): 36.34±4.09 vs. 35.26±3.82; Hb (g/L): 131.6±13.8 vs. 128.8±12.6; TLC (×109/L): 1.63±0.51 vs. 1.50±0.48, all P < 0.05]. The incidence of complications and mortality of the patients in metabolic vehicle group were lower than those of the formula group [40.0% (12/30) vs. 56.7% (17/30), 13.3% (4/30) vs. 16.7% (5/30) respectively, both P < 0.05]. After 2 weeks of nutrition support, the MAC of both groups increased compared with that before treatment, but there was no statistical significant difference in MAC in two groups (all P > 0.05). Conclusion Compared with the HB formula, the metabolic vehicle method can guide the daily energy intake of patients with severe coma more accurately. It is worthy to promote nutrition support program clinically guided by the metabolic vehicle one.