The objective of this study is to determine whether risk factor (RF) screening can be used instead of routine third-trimester testing for gonorrhea and chlamydia in a clinic setting. We performed prospective analysis of women entering prenatal care over a 10-month period. Patients included received combined gonorrhea and chlamydia screening by DNA probe at the first prenatal visit and in the third trimester. RF examined included age <20, marital status, history of sexually transmitted disease (STD) or hepatitis, drug use and gestational age at entry into prenatal care. Only women with negative initial screens were included in univariate and multivariate analyses. Five hundred forty-two women fulfilled study criteria. Sixty percent had 1 RF; 35% had a history of STD. Third-trimester screens were positive in 4.1%. The absence of RF had a negative predictive value of 99.1%. The sensitivity and specificity of RF screening was 90.9 and 40.7%, respectively (p = 0.003). The model of best fit was obtained using any positive RF and teen as independent variables (relative risk 6.9, 95% confidence interval 1.6-29.6, p = 0.01). In an urban clinic population, comprehensive RF screening is effective in predicting women at low risk for STD in the third trimester after an initial negative test.