Data from the International Lamotrigine Pregnancy Registry were analyzed to examine the effect of maximal first-trimester maternal dose of lamotrigine monotherapy on the risk of major birth defects (MBDs). Among 802 exposures, the frequency of MBDs was 2.7% (95% confidence interval [CI] 1.8-4.2%). The distribution of dose did not differ between infants with and those without MBDs (mean 248.3 milligrams per day [mg/day] and 278.9 mg/day, respectively, median 200 mg/day for both groups). A logistic regression analysis showed no difference in the risk of MBDs as a continuous function of dose (summary odds ratio [OR] per 100 mg increase =0.999, 95% CI 0.996-1.001). There was also no effect of dose, up to 400 mg/day, on the frequency of MBDs.