BACKGROUND: Nodal metastasis is considered a major prognostic factor in patients with ampulla of Vater carcinoma (AVC). No study has investigated the significance of the ratio between metastatic and resected/examined lymph nodes (LNR) in patients with AVC. METHODS: Demographic, operative, and pathology data, including number of resected/evaluated nodes and LNR, were collected from patients who underwent pancreaticoduodenectomy with radical intent for invasive AVC from 1990 to 2005. Survival rates and recurrence patterns were evaluated and predictors were identified. RESULTS: In 90 evaluable patients (51 males, 39 females, median age 62.5 years), 5-year disease-specific survival (DSS) was 61\%. The median number of resected/evaluated nodes was 16 (range: 5-47); 50\% of the patients had nodal metastases. The 5-year DSS according to LNR was 75\%, 49\%, 38\%, and 0\% for LNR = 0, LNR >0 and 0.2, and 0.4 (P = 0.002), respectively. The 5-year DSS was 81\% in patients with >16 resected/evaluated nodes compared with 45\% in those with 16 were significant predictors of survival; a number of resected/evaluated nodes >16 was also the only independent predictor of recurrence. CONCLUSIONS: After curative resection for AVC, LNR and a cutoff of 16 resected/evaluated nodes are powerful prognostic factors. LNR might represent a major parameter for patient stratification in adjuvant treatment trials.