Aim Limited data exist on Crohn's disease (CD)-associated small bowel adenocarcinoma (SBA). A large-scale retrospective cohort study was conducted comparing the clinical features and outcome of CD-associated SBA and de novo SBA. Method Data for patients with small bowel adenocarcinoma were gathered from the 1992-2010 United States Surveillance, Epidemiology and End Results cancer registry- Medicare linked database. We identified 2123 patients, of whom 179 had CD-associated and 1944 de novo SBA. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). Results CD-associated SBA was most commonly located in the ileum (62% vs 31%, P < 0.0001). CD patients were diagnosed at an earlier stage (I/II), compared with de novo SBA (55% vs 32%, P < 0.0001), and were more likely to undergo surgery (81% vs 72%, P = 0.0016). Chemotherapy use was similar (25% vs 21%, P = 0.1886). Patients with CD-associated SBA had better 5-year OS (43% vs 34%, P = 0.0121) but a similar CSS (65% vs 64%, P = 0.77). There was no difference in the OS between the cohorts when stratified by stage. On multivariate analysis, CD was not significantly related to OS [hazard ratio (HR) 0.97, 95% CI: 0.79-1.20, P = 0.7889]. Surgery and the extent of lymphadenectomy improved OS for all SBA patients (HR 0.73, 95% CI: 0.60-0.88, P = 0.001), whereas chemotherapy did not (HR 1.13, 95% CI: 0.99-1.28, P = 0.0665). Conclusion Patients with CD-associated SBA present at an earlier stage than patients with de novo SBA, they receive more surgery but similar rates of chemotherapy, and have similar OS and CSS. The presence of CD does not worsen survival after treatment of SBA.