OBJECTIVETo estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations.METHODSThis historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously.RESULTSBetween January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at theP< .05 level.CONCLUSIONWomen who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.