Background & Aims: This study aims to assess the application value of the real-time camera image-guided nasoenteric tube placement in critically ill COVID-19 patients undergoing endotracheal intubation and prone position ventilation therapy. Methods: We enrolled 116 COVID-19 patients receiving endotracheal intubation and prone position ventilation therapy in the intensive care unit (ICU). Patients were randomly divided into the real-time camera image-guided nasoenteric tube placement (n = 58) and bedside blind insertion (n = 58) groups. The success rate, placement time, complications, cost, heart rate, respiratory rate, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores were compared between the 2 groups. Results: For ICU patients with COVID-19 undergoing prone position ventilation therapy, the success rate and cost were significantly higher in the real-time camera image-guided group compared to the bedside blind group (P < .05). The placement time and complication incidence were significantly lower in the real-time camera image-guided group (P < .05). The differences in heart rate, respiratory rate, GCS scores, and APACHE-II scores were insignificant (P > .05). Conclusions: The real-time camera image-guided nasoenteric tube placement system had advantages for ICU COVID-19 patients undergoing prone position ventilation therapy, including a high success rate, short placement time, and no impact on patient position during tube placement. Real-time camera image-guided nasoenteric tube placement can be performed in any position, and demonstrates high efficiency, safety, and accuracy.