Introduction/Background: Harris County, TX, the 3rd most populous county in the nation, received its first travel-related Zika virus (ZIKV) case in December 2015. HCPHES immediately formed a Zika Readiness Team to address public health concerns and appropriate measures for Harris County. In the decision-making process to develop local policy, epidemiology investigation and analysis are critical. While additional cases are still being investigated, this analysis aims to: describe epidemiological characteristics of the confirmed cases; describe the county's rigorous mosquito surveillance and integrated vector management; discuss successes and challenges faced by a local health department in responding to ZIKV emergence in a region at high-risk for local transmission. Methods: Descriptive statistics were used to analyze the surveillance data of ZIKV in Harris County from December 2015 to present. Results: As of February 2016, fourteen investigations of suspected ZIKV infections were conducted and four of these were confirmed. Of the confirmed cases, one was a child, three were adults aged 21- 44, and two were female (none pregnant). All had recently traveled to El Salvador, and experienced illness onset during travel or within two days of return. Symptoms included rash (4, 100%), arthralgia (3, 75%), joint swelling (2, 50%), and fever (only the child). Symptoms resolved within 3 to 14 days of onset. Three (75%) of the patients always used mosquito repellent during travel, however, two of the three (67%) still noticed mosquito bites. All were tested for Zika, dengue, and chikungunya. The mean time from physician visit to case reporting was 18 days; turn-around time of test results was approximately 35 days after collection. A multidisciplinary Zika Readiness Team in HCPHES was immediately notified of cases for vector control, abatement, and preparedness. Discussion: With recent experience from the chikungunya outbreak in 2014, Harris County is well prepared for the emergence of ZIKV. Challenges to the county's public health response to Zika include: timing of confirmatory laboratory test results, capacity of available testing sites and resources, evolving understanding regarding the period of infectiousness, the possibility of sexual transmission, and protection of the local blood supply. Conclusions: Given the public health significance of ZIKV, and the vulnerability of many southern and gulf states to sustained local transmission, more research is imperative to address the aforementioned challenges.