In 2006, a cross-sectional survey of 384 randomly selected houses within a community-based follow-up study was conducted to assess the human T-cell lymphotropic virus (HTLV) prevalence in Bissau. Changes in prevalence and incidence rates were assessed based on a similar survey carried out 10 years earlier. The prevalence of HTLV-1 declined significantly from 3.5% in 1996 to 2.3% in 2006. The incidence between 1996 and 2006 was only 0.9/1000 person-years and tended to be higher for women than for men.