In 2015, Harris County (Texas) Public Health responded to the Zika virus (ZIKV) threat by investigating every report of potential ZIKV infection, including those with negative laboratory results, through December 2017. Before investigations, 40.6% of patients who were indicated for testing received it in accordance with Centers for Disease Control and Prevention guidelines. By investigating reports with negative ZIKV results, we increased the number of patients receiving correct and complete laboratory testing to 54.5%, and improved dissemination of evolving guidelines to partners across the health care spectrum.