Simple hepatitis B surface antigen (HBsAg) tests may facilitate ascertainment of hepatitis B virus (HBV) infection in settings with high endemicity but limited infrastructure. We evaluated two rapid HBsAg tests and characterized HBV coinfection in a Ghanaian HIV-positive cohort. Samples from 838 patients were tested by the rapid assays Determine and Vikia and the reference assays Architect, Murex version 3, and Liaison Ultra. The assays were also evaluated using the 2nd International Standard, a seroconversion panel, and two mutant panels. HBsAg-positive samples underwent HBV DNA quantification by real-time PCR and surface and polymerase gene population sequencing. Overall, 140/838 patients (16.7%; 95% confidence interval, 14.2 to 19.2%) were HBsAg positive, and of these, 103/140 (73.6%) were e-antigen negative and 118/140 (84.3%) showed an HBV DNA level of >14 IU/ml (median, 8,279 IU/ml). Assay sensitivities and specificities were as follows: Architect, 97.9 and 99.6%; Liaison, 97.1 and 99.4%; Murex, 98.6 and 99.3%; Determine, 69.3 and 100%; and Vikia, 70.7 and 100%. With Determine, the limit of detection was >1.5 to 3.4 HBsAg IU/ml, and the median HBV DNA loads were 598 and 10,905 IU/ml in Determine-negative and -positive samples, respectively (P = 0.0005). Results were similar with the Vikia assay. HBV DNA sequencing indicated infection with genotype E in 82/86 (95.3%) patients. HBsAg mutations affected assay performance, including a T123A mutant that escaped detection by Architect. Major drug resistance mutations were observed in 4/86 patients (4.6%). The prevalence of HBV coinfection was high in this HIV-positive Ghanaian cohort. The two rapid assays identified HBsAg-positive patients at risk for liver disease with high specificity, albeit with only moderate sensitivity.