Background/Aims: The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. Methods: From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. Results: The median survival was 5.7 months. The survival rate was 46.7% (14/30), 16.7% (5/30), 10% (3/30), and 6.7% (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-directed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). Conclusions: The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treatments improved patient survival.