Buoyancy disorders in sea turtles are common contributors to morbidity and mortality in the wild and are often encountered in rehabilitation facilities. The pathological gas accumulation that is the hallmark of this condition creates challenges for treatment, especially when concurrent systemic disease is present. These challenges increase with patient size, because anatomy and location of disease make gas evacuation more difficult using conventional methods when medical therapy alone is unsuccessful. This report discusses a novel technique using ultrasound-guided transplastron enterocentesis of the proximal gastrointestinal tract in an adult loggerhead sea turtle (Caretta caretta) with suspected partial intestinal obstruction. The sea turtle presented with positive buoyancy, and diagnostic imaging revealed gas accumulation in the gastrointestinal tract, as well as pneumonia. Medical therapy alone did not diminish the positive buoyancy or gastrointestinal distension. Ultrasound-guided transplastron enterocentesis was performed via the connective tissue lateral to the third inframarginal scute while the turtle was positioned with its left side raised, allowing any gas-filled intestine to be positioned laterally. Approximately 10.3 L of gas was evacuated from the proximal gastrointestinal lumen. Within 15 min of completing the procedure, the turtle was neutrally buoyant at the surface; it was resting comfortably on the bottom of the tank within 12 h. Thereafter, it continued to exhibit normal surfacing, diving, and resting behaviors. The turtle was released 111 days after enterocentesis to allow treatment of the concurrent pneumonia. Transplastron enterocentesis should be considered as a treatment option for buoyancy disorders in large adult sea turtles and for increasing the likelihood of release.