We present the preliminary results obtained by our research group utilizing Nd:YAG and diode lasers to treat Barrett's esophagus (BE). A total of 15 patients with BE (mean age 58 years) underwent endoscopic laser therapy: 11 with intestinal metaplasia, 2 with low-grade dysplasia, and 2 with high-grade dysplasia. The mean length of BE was 4 cm (range 1-12 cm). Six of these patients also underwent antireflux surgery, and nine were prescribed acid-suppressive medication. Endoscopic Nd:YAG laser treatment was carried out from 1997 to 1999; thereafter, diode laser was employed. The mean follow-up of these patients after the first laser session was 28 months. Patients underwent a mean of 6.5 laser sessions (range 3-17 sessions), with no apparent complications. The mean energy per session was 1705 JJ. Only six of these patients (40%) showed complete endoscopic and histologic remission, but a mean of 77% (SD 23.8%) of the total metaplastic tissue in all these patients was ablated. The percentage of healed mucosa was higher in patients with short-segment BE (92%) ( p < 0.05) and in subjects treated by two or more laser sessions per centimeter of BE length (89%) ( p < 0.05). All four patients with dysplasia showed histologic regression to nondysplastic BE or to squamous epithelium, without recurrence during a mean follow-up of 30 months. The patients who underwent antireflux surgery and those prescribed pharmacologic treatment had similar results. Nd:YAG and diode laser treatment of BE is a safe, effective procedure; it required two sessions per centimeter of metaplasia; and it achieved complete regression of the dysplasia. Further studies are necessary to quantify its effect on cancer incidence.