BACKGROUND Noninvasive assessment of esophageal varices (EV) may improve the management of patients with AND AIMS: cirrhosis and decrease both the medical and financial burden related to screening. In this multicenter, international study, our aim was to prospectively validate the use of the platelet count/spleen diameter ratio for the noninvasive diagnosis of EV. METHODS: A total of 218 cirrhotic patients underwent screening endoscopy for EV. Platelet count/spleen diameter ratio ((N/mm3)/mm) was assessed in all patients and its diagnostic accuracy was calculated. On the basis of previous results, a platelet count/spleen diameter ratio cutoff of 909 was applied to this population. The diagnostic accuracy of the platelet count/spleen diameter ratio was further evaluated for both severity and etiology of disease subgroups. RESULTS: Prevalence of EV was 54.1%. The platelet count/spleen diameter ratio had 86.0% (95% CI, 80.7–90.4%) diagnostic accuracy for EV, which was significantly greater as compared with either accuracy of platelet count alone (83.6%, 95% CI 78.0–88.3%, P = 0.038) or spleen diameter alone (80.2%, 95% CI 74.3–85.3%, P = 0.018). The 909 cutoff had 91.5% sensitivity (95% CI 85.0–95.9%), 67.0% specificity (95% CI 56.9–76.1%), 76.6% positive predictive value, 87.0% negative predictive value, 2.77 positive likelihood ratio, and 0.13 negative likelihood ratio for the diagnosis of EV. Accuracy of the platelet count/spleen diameter ratio was maintained for both severity and etiology of disease subgroups. CONCLUSIONS: The platelet count/spleen diameter ratio may be proposed as a safe and reproducible means to improve the management of cirrhotic patients who should undergo screening endoscopy for EV.