Recessive dystrophic epidermolysis bullosa (RDEB) is associated with high nutritional demands, esophageal strictures and dysphagia. About one quarter of the patients require gastrostomy tube placement to maintain adequate nutritional status. To minimize trauma to the skin and pharyngoesophageal mucosa caused by commonly used gastrostomy tube insertion techniques, we used a non-endoscopic, percutaneous, image-guided approach. This approach combines the use of ultrasound for mapping of the liver and spleen, water-soluble contrast enema to visualize the colon, and gastric insufflation to define the stomach. The gastrostomy tube is replaced by a low-profile button gastrostomy tube 10–12 weeks postoperatively. The five female patients reported in this series ranged in age from 6 to 9 years. They all tolerated the procedure well and no perioperative complications were encountered. All were able to tolerate feedings on postoperative day 1 and all underwent successful replacement of gastrostomy tubes by low-profile button tubes. Our experience suggests that a non-endoscopic, image-guided approach to gastrostomy tube placement offers a safe, effective, and minimally traumatic alternative to more commonly used approaches. It minimizes the risk of procedure-related morbidity and leads to overall improvement in the quality of life. As such, we strongly recommend that it be included in the treatment armamentarium for patients with epidermolysis bullosa and nutritional failure.