Goals: The role that vitamin B-12 deficiency plays in upper gastrointestinal motor dysfunction is not clear. The aim of this study was to determine whether B-12 replacement therapy improves prolonged gastric emptying time in dyspeptic patients with Helicobacter pylori infection. Materials and Methods: The study included 34 H. pylori-positive patients who had low serum levels of B-12 but had no other factors associated with altered gastric motility. Each patient underwent a radionuclide gastric emptying study before and after 3 months of B-12 replacement therapy. Dyspepsia scores were calculated pretherapy and posttherapy using a semiquantitative scale. A vitamin B-12 preparation (1,000 mug/d) was given intramuscularly for the first 10 days and then orally for 80 days. H. pylori eradication therapy was delayed for 3 months until the posttreatment radionuclide study was completed. Results: The mean gastric emptying time before B-12 treatment was significantly longer than that after treatment (230 +/- 190 minutes vs. 98 +/- 29 minutes, respectively; P < 0.0001). The mean dyspepsia score was also significantly improved by treatment (5.4 +/- 1.0 vs. 1.2 +/- 1.0, respectively; P < 0.0001). Conclusion: Vitamin B-12 deficiency appears to play an important role in the development of gastric dysmotility and its clinical consequences. Replacement therapy will improve gastric emptying in some patients with dyspepsia.