Two 18-month, randomised, double-blind trials have compared lamotrigine, lithium, and placebo as maintenance treatment in a total of 1315 recently manic or depressed patients with bipolar I disorder. Individual and combined analyses of these studies showed that both lamotrigine and lithium significantly prolonged the time to intervention for any mood episode compared with placebo. Lamotrigine was primarily effective against depression and lithium was primarily effective against mania. There was no evidence that lamotrigine induced mania/hypomania/mixed states, caused episode acceleration, or destabilised the overall course of illness. Lamotrigine was well tolerated, with a placebo-like adverse-event profile. In summary, lamotrigine is an effective and well-tolerated maintenance treatment for bipolar I disorder, providing a spectrum of efficacy complementary to that of lithium.