Gastric electrical stimulation (GES) treats refractory gastroparesis by delivering electric current, via electrodes, to gastric smooth muscle. Enterra therapy (Medtronic, Inc, Minneapolis, MN) uses an implantable neurostimulator with a high-frequency, low-energy output. We performed a controlled, multicenter, prospective study to evaluate the safety and efficacy of Enterra therapy in patients with chronic intractable nausea and vomiting from diabetic gastroparesis (DGP). Patients with refractory DGP (n = 55; mean age, 38 y; 66% female, 5.9 years of DGP) were given implants of the Enterra gastric stimulation system. After surgery, all patients had the stimulator turned on for 6 weeks and then they randomly were assigned to groups that had consecutive 3-month, cross-over periods with the device on or off. After this period, the device was turned on in all patients and they were followed up, unblinded, for 4.5 months. The median reduction in weekly vomiting frequency (WVF) at 6 weeks, compared with baseline, was 57% (P < .001). There was no difference in WVF between patients who had the device turned on or off during the cross-over period (median reduction, 0%; P = .215). At 1 year, the WVF of all patients was significantly lower than baseline values (median reduction, 67.8%; P < .001). Patients also had significant improvements in total symptom score, gastric emptying, quality of life, and median days in the hospital. In patients with intractable DGP, 6 weeks of GES therapy with Enterra significantly reduced vomiting and gastroparetic symptoms. Patients had improvements in subjective and objective parameters with chronic stimulation after 12 months of GES, compared with baseline. Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.