Infection with Burkholderia pseudomallei, the causative agent of melioidosis, is uncommon in the United States (U.S.), leading to delays in pathogen identification and clinical diagnosis which can often lead to laboratory exposures. The indirect hemagglutination assay (IHA) is the primary serological test for confirming exposure to B. pseudomallei. In the U.S., a titer of ≥1:40 suggests exposure to B. pseudomallei or a closely related species, and a 4-fold rise in IHA titer ≥1:40 with clinically compatible illness is considered diagnostically probable. A retrospective analysis of 160 voluntarily reported laboratory exposure events to B. pseudomallei across 29 U.S. jurisdictions and 5 countries between 2008–2024 was conducted. This analysis included post-exposure management data and IHA results for 855 exposed laboratory personnel who had serological monitoring performed at the U.S. Centers for Disease Control and Prevention (CDC). Among exposed laboratory personnel, 105 (12%) had a seropositive titer. Of these, ninety-one (87%) laboratory personnel remained seropositive (≥1:40) at their last IHA test. Five (1%) people had a 4-fold rise in titers, though none developed melioidosis. This report underscores the need for prospective studies to evaluate seropositive laboratory personnel and to update risk guidance for laboratory exposures in non-endemic areas.