Screening for subclinical herpes simplex virus type 2 (HSV-2) may be a useful adjunct in human immunodeficiency virus (HIV) care. However, HSV-2 serological tests have been suggested to perform less well in HIV-infected populations. In this study, HerpeSelect HSV-2 ELISA was compared with the Sure-Vue Rapid HSV-2 Test for HSV-2 screening of sera from 310 HIV-infected persons receiving care at an HIV-dedicated clinic in the Southeastern United States. In the study, assay agreement and whether the performance of both tests, rather than 1 test alone, would improve screening accuracy were determined. Overall percent test agreement was 96%. Negative percent agreement was best at a HerpeSelect index value <0.90 and positive percent agreement was best at a HerpeSelect index value ≥3.0 (97% and 100%, respectively). Using the manufacturer's established cutoffs for a HerpeSelect positive test result versus negative test result, discordant results between assays occurred in 4% of the cases, and the majority of these cases occurred when the HerpeSelect index value was between 0.9 and 2.9. These data suggest a good correlation between the HerpeSelect and the Sure-Vue HSV-2 Rapid Test in a U.S. HIV-infected population and suggest that confirmatory testing may not help in HSV-2 diagnosis except in cases where HerpeSelect index values are between 0.9 and 3.0. © 2013 Lippincott Williams & Wilkins.