Topiramate is a neuromodulatory agent increasingly prescribed for a number of neurological and non-neurological indications. Topiramate-treated patients are at risk for nephrolithiasis due to hypocitraturia and high urine pH. However, the prevalence of symptomatic stone disease in TPM users is generally perceived to be low. This study was undertaken to assess in topiramate-treated patients the prevalence of symptomatic nephrolithiasis (by history) and of asymptomatic nephrolithiasis by computed tomography (CT) scan. Topiramate users were identified from a database of patients with neurological disorders at a single university hospital. Among 75 topiramate-treated adult patients with a median daily dose of 300 mg and median treatment duration of 48 months, the prevalence of symptomatic nephrolithiasis was 10.7%. In a subset of topiramate-treated patients and no history of symptomatic stone disease, the prevalence of asymptomatic nephrolithiasis detected by CT scan was 20%. The prevalence of symptomatic nephrolithiasis with long-term topiramate use is higher than reported in short-term studies. Furthermore, clinical prevalence is underestimated due to asymptomatic nephrolithiasis.