A prospective, randomized clinical trial was conducted to study the safety and efficacy of the Cytobrush for Papanicolaou smear screens in 252 pregnant women. Two groups—Ayre spatula plus Cytobrush and Ayre spatula plus cotton swab—were compared. There was a higher incidence of spotting with each of the three devices as compared with studies of nonpregnant women. The highest incidence of spotting at time of exam occurred with the Cytobrush; however, this spotting was not clinically significant. Eleven first-trimester women experienced a pregnancy loss; five of these losses were due to a hydatidiform mole or missed abortion that occurred before the exam. Six women (2%) aborted spontaneously compared with a 10% incidence reported in the literature. It was concluded that all three devices are safe for use in pregnancy. In addition, the most adequate screen for retrieval of squamous epithelial cells was found to be the Ayre spatula, while the Cytobrush proved most effective for retrieval of endocervical epithelial cells.