Case reports have prompted concern that the use of bromocriptine mesylate to prevent lactation in the puerperium increases the risk of postpartum seizure. We conducted a record-based case-control study of postpartum seizures in three data bases to evaluate this relation. We identified 43 women who had a postpartum seizure, and we matched 319 controls individually by hospital of delivery, quinquenium of age, and time of delivery. Overall, women taking bromocriptine had a 22% lower risk for seizures, that is, the relative risk estimate was 0.78, with a 90% confidence interval of 0.29 to 1.87. A reduction in seizure risk is consistent with reports of antiseizure activity for bromocriptine in various species, including humans. We found a small positive association between bromocriptine use and seizures occurring more than 72 hours after delivery, with a relative risk estimate of 1.6 after controlling for seizure history. This association was offset by a strong negative association between bromocriptine use and early-occurring seizures. The pattern of an initial reduced risk followed by an increase to normal or above-normal levels of risk could result from an antiseizure activity of bromocriptine, with a rebound in risk when bromocriptine is withdrawn.