What is already known about this topic? Zika virus disease is an arboviral disease usually causing mild illness; however, congenital infection is associated with microcephaly and other birth defects. Although most cases in residents of U.S. states were travel-associated, local transmission has been reported. What is added by this report? In 2016, a total of 5,168 confirmed or probable cases of noncongenital Zika virus disease with symptom onset during January 1-December 31, 2016, were reported to ArboNET from U.S. states and the District of Columbia. Most (95%) cases were travel-associated. Locally acquired disease accounted for 4% of cases, with transmission occurring in Florida (218) and Texas (six). Forty-seven cases (1%) were acquired through other routes, including sexual transmission (45), laboratory transmission (one), and person-to-person through an unknown route (one). What are the implications for public health practice? CDC recommends that health care providers continue to test patients with a clinically compatible illness who live in or recently traveled to areas with ongoing Zika virus transmission or had unprotected sex with someone who lives in or traveled to those areas (https://www.cdc.gov/zika/hc-providers/ testing-guidance.html). Although the risk for travel-associated Zika virus disease appears to be decreasing, it is important that persons traveling to areas with a risk for Zika virus transmission continue to take precautions, including using strategies to prevent mosquito bites and sexual transmission.