This article describes the pattern of reported antidepressant use around the time of pregnancy in a population-based sample of women who delivered live-born babies without birth defects. Data were used from the National Birth Defects Prevention Study, an ongoing case-control study of risk factors for birth defects covering 10 US states. Mothers of live-born infants without birth defects (controls) born between 1998 and 2005 were randomly selected from each site. Information on the mother's characteristics and exposure to antidepressants was collected via a standardized telephone interview. Among 6582 mothers included in the study, 298 (4.5%) reported use of an antidepressant in the period of 3 months before through the end of pregnancy. Use of selective serotonin-reuptake inhibitors was reported most often (3.8%), followed by bupropion (0.7%). A statistically significant decline was observed, from 3.1% to 2.3% (P < .001), in reported use of antidepressants between the first and second month after conception. The frequency of reported antidepressant use at any time during pregnancy increased from 2.5% in 1998 to 8.1% in 2005 (P < .001) in 4 states. The findings show an increase in reported antidepressant use over a 9-year period and a substantial decrease in use around the usual time of pregnancy recognition.