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Background: In patients with cirrhosis the onset of clinically significant portal hypertension (CSPH; i.e., hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) is associated with an increased risk of complications. However, most cirrhotic patients already have CSPH at presentation, and limited information is available on further risk stratification in this population. This study assessed the prognostic value of a single HVPG measurement and Doppler-ultrasound (US) evaluation in patients with cirrhosis and CSPH. Methods: Eighty-six consecutive patients with cirrhosis (73% compensated) and untreated CSPH (mean HVPG 17.8 ± 5.1 mmHg) were included. All were studied by paired HVPG and US, and followed up for a minimum of 12 months (mean 28 ± 20 months). Results: Sixteen (25.3%) patients developed a first decompensation, and 11.6% died on follow-up. HVPG (per 1 mmHg increase OR 1.22, 95% CI 1.05-1.40, p = 0.007) and bilirubin (per 1 mg/ml increase OR 2.42, 95% CI 0.93-6.26, p = 0.06) independently predicted first decompensation, and Model for End-Stage Liver Disease (MELD) score (per 1 point increase OR 1.24, 95% CI 1.03-1.51, p = 0.03) and HVPG (per 1 mmHg increase OR 1.08, 95% CI 1.01-1.26, p = 0.05) independently predicted mortality. The best HVPG cutoff predicting these events was 16 mmHg. Ultrasonographic parameters lacked independent predictive value. The ultrasonographic detection of abdominal collaterals had a high positive likelihood ratio (7.03, 95% CI 2.23-22.16) for the prediction of HVPG ≥ 16 mmHg, implying an increase of the probability of belonging to this higher-risk population from 58 to 91%. Conclusions: HVPG holds an independent predictive value for first decompensation and death in patients with CSPH. The ultrasonographic detection of collaterals allows the non-invasive identification of patients with HVPG ≥ 16 mmHg, who are at higher risk. [ABSTRACT FROM AUTHOR]