Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is the preferred treatment for selected patients with mucinous appendiceal adenocarcinoma. Frequently, the hemidiaphragms are infiltrated with tumor, requiring partial diaphragm resection (DR) in order to obtain complete cytoreduction (CC-0). The clinical significance of diaphragmatic invasion and the optimum management to prevent transmission of disease from abdomen to chest is largely unknown. This was a retrospective review of 78 patients with mucinous appendiceal adenocarcinoma undergoing cytoreduction and partial DR at a single institution between 2010 and 2014. Partial DR was necessary in 31 (39.7%) patients in order to obtain CC-0. DR was not associated with increased morbidity or poor survival. Of the 31 patients who had a DR, 26 (83.9%) were treated with thoracoabdominal chemoperfusion. The remaining five (16.1%) patients had the diaphragm closed prior to HIPEC. Thoracoabdominal chemoperfusion was not associated with increased 30-day grade III/IV morbidity or respiratory complications. Overall, five (20%) patients with a DR developed thoracic recurrence. There were two (8%) thoracic recurrences in the 26 patients treated with thoracic chemoperfusion compared with three (60%) in the five patients who had their diaphragm closed prior to HIPEC (p=0.002). In univariate analysis histology, CC-0 and thoracoabdominal chemoperfusion were associated with thoracic disease-free survival; however, none of these were significant on multivariate analysis. DR is not associated with increased morbidity and should be performed, if needed, to obtain a CC-0. Following DR, patients remain at significant risk of developing thoracic recurrence. Thoracoabdominal chemoperfusion reduces this risk without increasing morbidity.