Objective To evaluate the clinical implementation value of bedside ultrasound monitoring of gastric residual volume in the guidance of enteral nutrition (EN) in severe patients with mechanical ventilation. Methods One hundred and forty-three patients undergoing nasal feeding EN and mechanical ventilation ≥ 72 hours in the Department of Intensive Care Unit (ICU) of Jinhua People's Hospital from May 2017 to August 2018 were enrolled, and they were randomly divided into two groups: a traditional control group (71 cases) and an ultrasound monitoring group (72 cases). The traditional control group applied 50 mL syringe to withdraw gastric juice from gastric tube, once every 4 hours, and then the EN protocol based on the gastric residual volume was adjusted; the ultrasound monitoring group used bedside ultrasound to monitor the gastric residual volume once every 4 hours, and then the EN protocol was adjusted accordingly. The changes of EN tolerance indexes e.g. abdominal distension, reflux vomiting, diarrhea, bowel sound hyperactivity or disappearance, intra-abdominal pressure, etc, the changes of incidence of ventilator-associated pneumonia (VAP), mechanical ventilation time and ICU hospitalization time in these two groups were observed. Results The incidences of abdominal distension, reflux vomiting, diarrhea, intestinal hyperactivity or disappearance of bowel sounds were significantly lower in the ultrasound monitoring group than those in the traditional control group [abdominal distension: 23.6% (17/72) vs. 28.2% (20/71), reflux vomiting: 18.1% (13/72) vs. 22.5% (16/71), diarrhea: 13.9% (10/72) vs. 14.1% (10/71), bowel sounds hyperactivity or disappearance: 9.7% (7/72) vs. 11.3% (8/71), all P < 0.05], the intra-abdominal pressure was obviously lower in the ultrasound monitoring group than that in the traditional control group [mmHg (1 mmHg = 0.133 kPa): 8.9±5.6 vs. 9.6±6.1, P < 0.05], and the incidence of VAP was significantly lower in the ultrasound monitoring group than that in the traditional control group [19.7% (14/72) vs. 23.9% (17/71), P < 0.05], the mechanical ventilation time and ICU hospitalization time were also significantly shorter in the ultrasound monitoring group than those in the traditional control group [mechanical ventilation time (days): 10.1±3.1 vs. 12.2±3.4, ICU hospitalization time (days): 16.8±4.2 vs. 20.6±4.8, all P < 0.05]. Conclusion The bedside ultrasound monitoring gastric residual volume can improve EN tolerance, reduce VAP incidence, and shorten the mechanical ventilation time and ICU hospitalization time in patients with mechanical ventilation.