BackgroundLong‐term administration of TDF/ETV in patients with HBV‐related compensated cirrhosis reduces HCC and decompensation events but the effect of this regimen on development/regression of oesophageal varices (EV) is currently unknown.AimTo assess the risk of EV development/progression in this population.MethodsA total of 186 Caucasian HBV‐monoinfected compensated cirrhotics were enrolled in a long‐term cohort study from TDF/ETV introduction. Upper GI endoscopies were performed according to Baveno recommendations. Primary endpoint was development/progression of oesophageal/gastric varices over time.ResultsAt TDF/ETV start, median age was 61 years, 80% males, 60% HBV‐DNA undetectable, 63% NUCs previously exposed, 73% normal ALT, 40% platelets <150,000/mmc and 25 (13%) with low‐risk varices (LRV). During 11 years of antiviral therapy and 666 endoscopies performed, 9 patients either developed or had a progression of oesophageal or gastric varices with an 11‐year cumulative probability of 5.1% (95% CI 3–10%); no patient bled. Out of 161 patients without EV at baseline, the 11‐year probably was 4.5% with all varices developing within the first six years of treatment. In 25 patients with LRV at baseline, the 11‐year probability of progression or regression was 9.3% and 58%, respectively. Only baseline platelet count (HR 0.96, p = 0.028) was associated with LRV development at multivariate analysis: platelet ≤90,000/mmc (AUROC 0.70) had 98.1% specificity, 42.9% sensitivity, 50% PPV for LRV onset.ConclusionsIn compensated cirrhotic patients under long‐term effective TDF/ETV treatment, the 11‐year risk of developing/progressing EV is negligible, thus challenging the current endoscopic surveillance recommendations in patients without EV at baseline.