Introduction: Viral hepatitis B (VHB) is a serious and global public health issue, particularly in sub-Saharan Africa where it is endemic. The objective of this work was to evaluate the effectiveness and safety of tenofovir disoproxil fumarate (TDF) in the treatment of chronic VHB in Cotonou. Methods: This was a descriptive cross-sectional study with a retrospective collection of data from January 1st, 2015 to December 31st, 2016 (24 months) and prospective from May to August 2017 (4 months). Chronic VHB patients treated with TDF for at least 6 months were included. The non-detectability of HBV DNA and the normalization of aminotransferases defined the virological and biochemical responses, respectively. The evaluation of the treatment response on liver fibrosis was done by using APRI score. Renal impairment was assessed by a reduction in glomerular filtration rate according to MDRD (Modifications of the Diet in Renal Disease) formula below 90 mL/min/1.73 m 2. Results: In all, 42 patients treated with TDF were included. The average age was 46.7 ± 13.8 years. The study population was predominantly male with a sex ratio of 2.5. Among the 42 patients treated with TDF for an average of 60 weeks (24 to 96 weeks), 36 patients (85.7%) had a virological response; 21 patients (50%) had a biochemical response. Virologic response was 70% at week 24 (W24), 92.6% at W48, 87.5% at W72 and 100% at W96 without significant difference between W24 and W48; between W48 and W72 then between W72 and W96. There was a regression of fibrosis and cirrhosis but not significantly. Renal involvement occurred in 3 out of 19 cases (15.