Background Zika virus infection during pregnancy is a known cause of congenital microcephaly and other neurologic morbidities. Objective We present the results of a large-scale prenatal screening program in place at a single-center health care system since March 14, 2016. Our aims were to report the baseline prevalence of travel-associated Zika infection in our pregnant population, determine travel characteristics of women with evidence of Zika infection, and evaluate maternal and neonatal outcomes compared to women without evidence of Zika infection. Study Design This is a prospective, observational study of prenatal Zika virus screening in our health care system. We screened all pregnant women for recent travel to a Zika-affected area, and the serum was tested for those considered at risk for infection. We compared maternal demographic and travel characteristics and perinatal outcomes among women with positive and negative Zika virus tests during pregnancy. Comprehensive neurologic evaluation was performed on all infants delivered of women with evidence of possible Zika virus infection during pregnancy. Head circumference percentiles by gestational age were compared for infants delivered of women with positive and negative Zika virus test results. Results From March 14 through Oct. 1, 2016, a total of 14,161 pregnant women were screened for travel to a Zika-affected country. A total of 610 (4.3%) women reported travel, and test results were available in 547. Of these, evidence of possible Zika virus infection was found in 29 (5.3%). In our population, the prevalence of asymptomatic or symptomatic Zika virus infection among pregnant women was 2/1000. Women with evidence of Zika virus infection were more likely to have traveled from Central or South America (97% vs 12%, P < .001). There were 391 deliveries available for analysis. There was no significant difference in obstetric or neonatal morbidities among women with or without evidence of possible Zika virus infection. Additionally, there was no difference in mean head circumference of infants born to women with positive vs negative Zika virus testing. No microcephalic infants born to women with Zika infection were identified, although 1 infant with hydranencephaly was born to a woman with unconfirmed possible Zika disease. Long-term outcomes for infants exposed to maternal Zika infection during pregnancy are yet unknown. Conclusion Based on a large-scale prenatal Zika screening program in an area with a predominantly Hispanic population, we identified that 4% were at risk from reported travel with only 2/1000 infected. Women traveling from heavily affected areas were most at risk for infection. Neonatal head circumference percentiles among infants born to women with evidence of possible Zika virus infection during pregnancy were not reduced when compared to infants born to women without infection.