BACKGROUND: Prevalence of occult hepatitis B infection (OBI) and its clinical outcomes have been poorly studied in Africa. METHOD: Using the PROLIFICA cohort, we compared the prevalence of OBI between HBsAg-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases) and estimated the population attributable fraction for the effect of OBI on advanced liver disease. RESULTS: OBI prevalence was significantly higher among the cases (15/82, 18.3%) than in the control group (31/330, 9.4%, p=0.03). Among participants with OBI, pre-S2 mutations were detected in 5/31 (16.1%) controls and 3/14 (21.4%) cases (p=0.7).After adjusting for age, sex, and anti-HCV serology, OBI was significantly associated with advanced liver disease [OR: 2.8 (95% CI: 1.3-6.0), p=0.006]. In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (7.5-18.1%) and 16.9% (15.2-18.6%), respectively. CONCLUSION: OBI is endemic and an independent risk factor of advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg-positivity.