We conducted a pilot study to evaluate the efficacy of topiramate in trigeminal neuralgia using a randomized, double-blind, placebo-controlled, two-period crossover design. Three patients were enrolled in and completed the study. All three patients responded to topiramate in this main study and entered a subsequent confirmatory study consisting of three topiramate-placebo crossovers. In the main study, topiramate reduced pain by 31%, 42%, and 64% in the three patients (p = 0.04). However, topiramate showed no effect in the confirmatory study. Given that trials of less common pain conditions are fraught with low patient recruitment rates, a multiple crossover design provides more information, which is important in conditions associated with considerable pain fluctuation. Larger trials are needed to more precisely estimate the effect of topiramate in trigeminal neuralgia.