Abstract Background Barrett's esophagus (BE) is a premalignant pathology that can sometimes progress to adenocarcinoma (ADC) of the esophagus. Although the percentage of malignancy is low, one in every 200 patients/year, in the world literature there is great variability (0,1-1 % patients/year). This important discrepancy arises because we know that not all patients with BE have the same risk of malignancy. The objective of this work is allowing us to stratify patients according to their risk of malignancy. Methods We have 147 patients with a mean (range) follow-up is 13.3 years (2-33). During this period, 16 patients progressed to early esophageal ADC (10.8%), malignancy rate of 0.8 patients/year. Two study groups were obtained: 1. Patients with non-malignant BE: 131 (median age 43 years (10-79). 96 men (73%). 2. Patients with malignant BE: 16 (median age 51 years (21-74). 15 men (94%). Statistical method A univariate and multivariate statistical study was carried out to detect which factors have a greater risk of malignancy. We analyzed epidemiological, clinical, endoscopic, histological, functional factors (motility and pH) and therapeutic. RESULTS Age: 22 patients over 65 years, 22.7% of malignancy, and only 8.8% patients under 65 (p=0.05, OR=3.048). Sex 13.5 % men progressed and only 2.8 % women (p=0.045). Familial Barrett's esophagus was positive in 6 patients, 66.6% malignant, while only 8.5% without familial BE progressed (p=0.0001). EB length: patients with metaplastic segments greater than 4 cm have a 12 times greater risk of malignancy. Low grade dysplasia: 39 % patients had a diagnosis of LGD became malignant, and only 7 % patients with not LGD (p<0.0001, OR 8.49). Proliferation Ki67 and p53 high expression patients were malignant in 69.2% and 91.7 % (p<0.0001, OR 29.25 and 242.00). Esophageal functional studies 22.6% patients with esophageal body hypomotility became malignant and only 3.2 % with preserved esophageal body motility (p=0.001, OR 8.75). Neither the mean LES pressure nor the percentage of patients with hypotensive LES were statistically significant. 20.4% patients with severe acid reflux (pH <4 greater than 24%) became malignant versus 6.1 % patients suffered from less reflux (p=0.009, OR 3.93). Type and effectiveness of treatment Malignancy according to treatment, no differences are observed (10 % and 11.6 % en medical and surgical groups). Only 3.9 % patients with effective treatment became malignant, while in 48.1% who failed treatment (p=0.0001, OR 22.9). Multivariate analysis Only LGD reached statistical significance (p=0.007) with an OR 7.18, and the high expression of p53 (p<0.0001) with an OR 89.14. Risk groups Based on statistical analysis, we have established three risk groups (figure 1). We included 5 patients with High Risk (3.5%, F-U 8.6 years), all malignant (100%, 11.6% patients/year). Intermediate Risk 33 patients (22.5%, F-U 11.97 years, with progression in 11 patients (33.3%, 2.7% patients/year). Low Risk to 109 patients (74%), none became malignant. (p<0.0001, OR: 1.78). Conclusion In patients with high and intermediate risk, therapeutic options and endoscopic follow-up should be different than in patients with the absence of these disease characteristics, classified as low risk.