The purpose of this study was to investigate the feasibility of a flat-detector C-arm-guided radiographic technique (cone-beam computed tomography [CBCT]) for percutaneous radiologic gastrostomy (PRG) insertion. Eighteen patients (13 men and 5 women; mean age 62 years) in whom percutaneous endoscopic gastrostomy (PEG) had failed underwent CBCT-guided PRG insertion. PEG failure or unsuitability was caused by upper gastrointestinal tract obstruction in all cases. Indications for gastrostomy were esophageal and head and neck malignancies, respectively. Before the PRG procedure, initial C-arm CBCT scans were acquired. Three- and 2-dimensional soft-tissue reconstructions of the epigastrium region were generated on a dedicated workstation. Subsequently, gastropexy was performed with T-fasteners after CBCT-guided puncture of the stomach bubble, followed by insertion of an 14F balloon-retained catheter through a peel-away introducer. Puncture of the stomach bubble and PRG insertion was technically successful in all patients without alteration of the epigastric region. There was no malpositioning of the tube or other major periprocedural complications. In 2 patients, minor complications occurred during the first 30 days of follow-up (PRG malfunction: n = 1; slight infection: n = 1). Late complications, which were mainly tube disturbances, were observed in 2 patients. The mean follow-up time was 212 days. CBCT-guided PRG is a safe, well-tolerated, and successful method of gastrostomy insertion in patients in whom endoscopic gastrostomy is not feasible. CBCT provides detailed imaging of the soft tissue and surrounding structures of the epigastric region in one diagnostic tour and thus significantly improves the planning of PRG procedures.