To evaluate the efficacy and safety of gabapentin in the treatment of muscle cramps, we engaged an open-label trial with a group of 30 patients with frequent (>5 cramps/week), stable, long-lasting cramps, associated with different diseases. Gabapentin was effective in reducing the frequency and severity of muscle cramps and associated sleep disturbances (clinical outcome measures) within the first 2 weeks of medication at 600 mg/d. At the 1 month control (mean dosage, 825 ± 35 mg), almost every patient had responded to treatment and two thirds experienced a total remission of symptoms. After 3 months of therapy (mean dosage, 892 ± 180 mg), cramps disappeared in 100% of patients and this benefit persisted as long as 6 months. Additionally, we evaluated in 10 patients the Cramps Threshold Frequency (CTF) (neurophysiological outcome measure) before and during gabapentin treatment. Gabapentin significantly increased the CTF, returning it to normal values. With the limitation of an open-label methodology, our clinical and neurophysiologic experience suggests that a gabapentin dose of 600–1200 mg/d would be helpful in the treatment of muscular cramps.