Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes; symptoms of infection include rash, arthralgia, fever, and conjunctivitis.*,† Zika virus infection during pregnancy can cause microcephaly and other serious brain anomalies (1), and in rare cases, Zika virus infection has been associated with Guillain-Barré syndrome (2) and severe thrombocytopenia (3). This report describes the incidence of reported symptomatic Zika virus disease in the U.S. territory of Puerto Rico by age and sex. During November 1, 2015-October 20, 2016, 62,500 suspected Zika virus disease cases were reported to the Puerto Rico Department of Health (PRDH); 29,345 (47%) were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing, or were presumptively diagnosed based on serological testing. The highest incidence among confirmed or presumptive cases occurred among persons aged 20-29 years (1,150 cases per 100,000 residents). Among 28,219 (96.2%) nonpregnant patients with confirmed or presumptive Zika virus disease, incidence was higher among women (936 per 100,000 population) than men (576 per 100,000) for all age groups ≥20 years, and the majority (61%) of reported Zika virus disease cases occurred in females. Among suspected Zika virus disease cases in nonpregnant adults aged ≥40 years, the percentage that tested positive among females (52%) was higher than that among males (47%) (p<0.01). Reasons for the higher incidence of Zika virus disease among women aged ≥20 years are not known; serosurveys of persons living near confirmed Zika virus disease cases might help to elucidate these findings. Residents of and travelers to Puerto Rico should remove or cover standing water, practice mosquito abatement, employ mosquito bite avoidance behaviors, take precautions to reduce the risk for sexual transmission, and seek medical care for any acute illness with rash or fever.