A 35-year-old male presented to the emergency department (ED) with intermittent shortness of breath and right upper quadrant pain associated with significant bloating following meals. He reported multiple previous ED visits for the same symptoms. The patient’s other significant medical conditions included asthma, obesity, and seropositive rheumatoid arthritis being treated with disease-modifying anti-rheumatic drugs and systemic steroids. The patient gave a history of a motor vehicle crash several years ago. The patient was the front seat passenger of a vehicle which was struck on his side by an incoming vehicle. The patient reported that a computed tomography (CT) scan done at the time revealed only several broken ribs, but he recalled no mention of a diaphragmatic injury. Chest radiograph showed a significant elevation of the right hemidiaphragm and mild resultant leftward shift of the mediastinum. A CT of chest, abdomen, and pelvis showed a 15- by 10-cm right diaphragmatic defect resulting in the intrathoracic herniation of the entire liver, the gallbladder, the hepatic flexure of the colon, and the descending duodenum. There was no evidence of bowel obstruction or gallbladder pathology. At the time of the initial diagnosis of the diaphragmatic hernia, the patient was being treated with 10 mg of oral prednisone twice a day for rheumatoid arthritis. Given his stable clinical picture, lack of obstructive symptoms, and the high dose of scheduled systemic steroids, the patient was discharged home and prepared for surgery. After weaning him down to 2 mg of oral prednisone twice daily, the patient underwent an elective surgical repair. Given the complexity of the altered anatomy, the procedure was carried out using a combined hand-assisted thoracoscopic-laparoscopic approach. Initially, a 5-mm Covidien Visiport Plus (Medtronic, Minneapolis, MN) optical trocar was placed under vision in the right upper quadrant, and the abdomen was insufflated to 15 mm Hg. Three additional 5-mm ports were placed in the right upper quadrant. On laparoscopy, a large hernia defect was apparent in the right hemidiaphragm. The liver was absent from its anatomical position and could not be visualized through the defect. After the removal of adhesions around the perimeter of the hernia, traction was applied to the omentum to reduce it into the abdominal cavity. The reduction of the omentum also led to the reduction of the colon and stomach into the abdominal cavity without additional effort, and the liver could be visualized in the right thoracic cavity through the diaphragmatic defect, along with an atrophic right lung. At this point, a subcostal incision was made connecting the initial two port sites, and a hand port was placed. The diaphragmatic defect was extended laterally (with care taken to avoid damaging the posterolateral branch of the phrenic nerve) to assist in the subsequent adhesiolysis. The liver was palpated, and gentle traction applied so that adhesions could be taken down. A single thoracoscopic port was placed to allow a better visualization during this phase of the procedure. Once the liver was free of intrathoracic adhesions, it was gently pulled down and reduced to its anatomical position and the remaining hernial sac was resected. Repair of the diaphragmatic defect began from lateral to medial via an abdominal approach using interrupted Ethibond (Ethicon, Somerville, NJ) polyester sutures, but once the diaphragm could no longer be well approximated, a combined thoraco-abdominal approach was required. A 7-cm lateral incision was made by extending the thoracoscopic port site into the eighth intercostal space, and a segment of the eighth rib was resected. The liver was palpated and retracted through the abdominal hand port to allow for better exposure of the diaphragm, while the remaining approximation of the diaphragmatic rupture was completed via the thoracic approach. The repair was reinforced with a 10 × 15-cm Covidien ProGrip (Medtronic, Minneapolis, MN) synthetic mesh that was applied and tacked into place laparoscopically from the abdominal side. Operative time was 220 min and the total estimated blood loss was 100 mL. The patient had an uneventful post-operative course. Post-operative chest radiograph showed a good anatomical repair. He was discharged on the eighth post-operative day on a regular diet. Six months after the procedure, the patient is doing well and shows no evidence of recurrence.