Infection with the soil-transmitted helminth Strongyloides stercoralis is typically asymptomatic but can result in life-threatening hyperinfection syndrome in immunocompromised individuals. To improve serological tests for strongyloidiasis, we evaluated the Ss-IR antigen using a multiplex bead assay and compared this assay to the commonly used Ss-NIE antigen. We assessed assay sensitivity and specificity using the following serum panels: sera from United States-bound refugees (57 positive stool polymerase chain reaction [PCR], 88 negative PCR) departing from Thailand-Burma border camps (panel 1); sera from individuals from Argentina with stool PCR confirmed S. stercoralis (panel 2, n = 50); and presumed negatives from the United States with no travel history (panel 3, n = 185). The Ss-IR antigen demonstrated sensitivities of 90.0% and 89.5% and specificities of 98.9% and 89.8% in panels 1, and panels 2 and 3, respectively. When compared with Ss-NIE, the Ss-IR antigen demonstrated superior sensitivity, area under the curve, and reproducibility than Ss-NIE, supporting more extensive validation for surveillance use.