Introduction: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignancy associated with poor outcomes. Recent reports have shown longer survival with radical surgery, usually combined with intraperitoneal chemotherapy. However, surgical interventions in these patients have not been extensively studied at a population level. The objective of this retrospective cohort study is to assess the prevalence of surgical and nonsurgical interventions for DMPM patients, the influence of surgery on survival outcomes, and the associations between demographic and clinical factors with treatments and outcomes. Methods: This study included adult patients diagnosed with DMPM from 2003 to 2014 and registered in the National Cancer Database (NCDB). The primary outcome was overall survival. Histologically confirmed mesothelioma was defined using International Classification of Diseases (ICD)-3 codes 9050/3, 9051/3, 90523, and 9053/3 and peritoneum as primary affected organ using ICD codes C17-19, C22-24, C26, C42, C48, and C76. Relationships between demographic and clinical variables, surgical treatments, and survival outcomes were evaluated using logistic and Cox modeling and log-rank tests. Results: A total of 2062 patients were identified, of whom 1055 (51%) did not receive any surgery while 701 (34%) received radical surgery. Patients receiving radical surgery had overall survival of 38.4 months compared with 7.1 months for patients without surgery (p < 0.001) and 41.8 months in patients who received both radical surgery and systemic chemotherapy. Conclusions: Patients selected for and treated with radical surgery had significantly better overall survival compared with those receiving nonsurgical treatment. Patients newly diagnosed with DMPM should be evaluated for the possibility of receiving radical surgery.