BACKGROUND: Functional dyspepsia (FD) is common but few efficacious therapies exist. Itopride, a prokinetic, acts via dopamine D2 receptor antagonism and acetylcholinesterase inhibition, and is now approved in Japan, Mexico, and Europe for FD. However, long-term efficacy and safety data have not been published. OBJECTIVE: To evaluate the long-term safety and potential effectiveness of itopride. DESIGN: A long-term open-label drug effectiveness study. METHODS: Males and females, 18-65 years, with FD (Rome II) and the absence (by upper endoscopy) of any relevant structural disease were recruited. After the double-blind treatment phase, patients were treated in an open-label extension phase. RESULTS: A total of 798 patients were included in these two open-label trials and received at least one dose of study medication; 551 patients (69.0%) completed 6 months of treatment, and 294 patients (36.8%) completed a 12-month period. Response rates based on the global physician assessment were 61.7%, 64.8%, 69.0 %, 69.1%, 70.1%, 73.1%, and 77.9% at weeks 8, 16, 24, 32, 40, 48, and 52, respectively. Compliance was above 95%. The safety and tolerability profiles were as expected, with the majority of adverse events being gastrointestinal. Prolactin elevations occurred in 3% of the cases but were not clinically significant. No ECG changes were identified. CONCLUSION: In this population, itopride, given for up to 12 months, was safe, and up to two-thirds appeared to maintain symptom benefit. TRIAL REGISTRATION: NCT00110968 and NCT00112203.