The use of prescription opioids is becoming an increasing problem among women of reproductive age. More than half of pregnancies are unintended; therefore, many first-trimester exposures to opioids occur before pregnancy confirmation. Studies are limited about the fetal risks to opioid exposure in early pregnancy. One large study demonstrated an increased risk of certain heart defects and spina bifida with first-trimester exposure to opioids. It is important to counsel women whose fetuses were exposed to opioids in early pregnancy about the potential risks, encourage them to cease using opioids or seek alternative treatments when appropriate, and use the lowest effective dose when opioid treatment is to be continued. It is also valuable to screen for anatomic abnormalities such as neural tube and cardiac defects with available maternal serum testing and ultrasound imaging in the early second trimester. Birth Defects Research (Part A) 94:620–625, 2012. © 2012 Wiley Periodicals, Inc.