Objective To investigate the clinical efficacy of implementation of standardized enteral nutrition (EN) and its effects on prognosis in patients with severe traumatic brain injury (sTBI) undergoing mechanical ventilation (MV). Methods Eighty-eight patients with sTBI undergoing MV admitted to the Department of Critical Care Medicine of Yuyao People's Hospital from January 2016 to December 2017 were enrolled, they were divided into a control group (42 cases) and an experiment group (46 cases) depending on the demarcation timing of January 1, 2017, the beginning time of implementing standardized EN. All the patients received early EN and conventional treatment in the two groups. Additionally, the procedure of standardized EN was implemented in the experiment group. The differences in starting time of EN, the first defecation time, the rates of EN therapeutic energy and protein supply reaching their respective targets, duration of MV and ICU stay and 28-day mortality were compared between the two groups. Results The starting time of EN (hours: 25.61±8.74 vs. 32.79±8.63) and first defecation time (days: 3.03±0.79 vs. 3.61±0.89) were significantly earlier in the experiment group than those in the control group (both P < 0.05); the rates of energy and protein supply reaching the respective targets on the 5th day and 7th day after receiving EN were all significantly higher in the experiment group than those in the control group [rates of energy supply reaching target on the 5th day: (44.83±13.99)% vs. 37.59±10.88, and on the 7th day: (68.07±10.68)% vs. (62.69±9.87)%; rate of protein supply reaching target on the 5th day: (31.93±9.49)% vs. (27.06±8.08)%, and on the 7th day: (62.09±9.91)% vs. (54.55±11.27) %, all P < 0.05]; the durations of MV (hours: 9.24±2.91 vs. 10.67±3.41) and ICU stay (days: 12.09±3.37 vs. 13.93±4.98) in the experiment group were significantly shorter than those in the control group (all P < 0.05). No statistical significant difference in the 28-day mortality was observed between the experiment group and control group [21.74% (10/46) vs. 19.05% (8/42), P > 0.05]. Conclusion The efficacy of implementation of standardized EN in patients with sTBI undergoing MV is very significant, as it can significantly improve the rate of reaching EN target, and shorten the duration of MV and ICU stay.