Objective To study the influence of clinical nutritional support on the effects of mechanical ventilation (MV), and to find the factors affecting the outcome of patients undergoing MV. Methods A case-control study was conducted. The clinical data of 235 patients undergoing MV admitted to intensive care unit (ICU) of Tongde Hospital of Zhejiang Province from January 2015 to June 2017 were retrospectively analyzed. The patients were divided into two groups according to whether weaning successfully within 7 days. The clinical data of patients in the two groups were collected including gender, age, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, underlying disease, nutritional indicators, nutritional support, and complications. The outcome of withdrawal within 7 days was served as a dependent variable, all observed indicators were served as independent variables, and Logistic regression analysis was carried out to screen the influencing factors of the weaning results within 7 days. Results 235 patients undergoing MV were enrolled, 128 patients were successfully withdrawn within 7 days, and 107 were unsuccessfully withdrawn. Compared with the successful weaning group, the patients of weaning failure group were older, and had higher APACHEⅡ score and lower albumin (Alb) and hemoglobin (Hb), more patients with internal medical underlying diseases and receiving parenteral nutrition (PN) and mixed nutrition, and the incidences of secondary infection, vomiting, abdominal distension, abnormal bowel sound, gastric retention, and diarrhea were higher. However, there was no statistical significance in gender between the two groups. The variables of statistical significance in univariate analysis were enrolled in the multifactor analysis model showing that age [odds ratio (OR) = 1.269, 95% confidence interval (95%CI) = 1.119-1.439, P < 0.001], APACHEⅡ score (OR = 1.643, 95%CI = 1.423-1.897, P < 0.001), internal medical underlying diseases (OR = 6.298, 95%CI = 4.012-9.887, P < 0.001), secondary infection (OR = 8.323, 95%CI = 2.568-26.975, P < 0.001), abdominal distension (OR = 3.368, 95%CI = 1.586-7.152, P = 0.002), abnormal bowel sounds (OR = 2.856, 95%CI = 1.215-6.713, P = 0.017), gastric retention (OR = 1.996, 95%CI = 1.183-3.368, P = 0.010), diarrhea (OR = 3.035, 95%CI = 1.337-6.890, P = 0.008) were risk factors for unsuccessful weaning,and compared with PN, enteral nutrition (EN; OR = 0.191, 95%CI = 0.098-0.372, P < 0.001) and mixed nutrition (OR = 0.375, 95%CI = 0.150-0.938, P = 0.037) were protective factors of successful weaning. The gender, Alb and Hb before and after MV, vomiting, gastrointestinal hemorrhage were not associated with weaning outcome within 7 days. Conclusions Elder, high APACHEⅡ score, internal medical underlying diseases, or secondary infection, abdominal distension, abnormal bowel sounds, gastric retention, diarrhea were risk factors of weaning failure within 7 days in patients undergoing MV. Compared with PN, EN and mixed nutrition were protective factors for successful weaning. For patients undergoing MV, EN should be performed early in the case of full recovery, hemodynamic stability, and serious metabolic disorders.