Critical donor selection and testing increases the safety of blood transfusion by excluding donors at risk of transmitting infections. This study investigated the seroprevalence of and risk factors for sexually transmitted infections (STIs) among accepted and deferred blood donors in Jamaica. A total of 1015 blood donors consisting of 794 (78%) accepted donors and 221 (22%) deferred donors presenting at the Central Blood Bank, Jamaica, over a six-month period, were recruited for this study. A standardized questionnaire was administered to each participant and a sample of blood obtained for detection of hepatitis B surface antigen, antibodies to Treponema pallidum, human immunodeficiency virus (HIV) and human T-cell lymphotrophic virus type-1 (HTLV-1). Deferred donors were three times more likely to be seropositive for STI than accepted donors (16.3% vs 5.2%, OR 3.57, 95% CI 2.16 - 5.90, p < 0.0001). Males had significant association between STI seropositivity and having fathered children with two or more women (p = 0.0085), unprotected sexual intercourse with several persons (p = 0.0326), and history of genital herpes (p = 0.0121). Significant risk factors identified among females were unprotected sex with several partners (p = 0.0385); having more than ten lifetime partners (p = 0.0105); and use of depoprovera (p = 0.0028). This study confirms higher rates of STI among deferred blood donors and supports the donor deferral system in Jamaica.