The importance of blood flow in duodenal ulcer healing is unclear. Endoscopic reflectance spectrophotometry measures the index of oxygen saturation (ISO2), which is significantly correlated with blood flow. In 97 consecutive patients who presented with duodenal ulcer bleeding, the difference in the index of oxygen saturation (delta ISO2: ulcer margin ISO2 minus adjacent mucosa ISO2) was determined during the initial endoscopic examination. Endoscopic examinations were repeated until the ulcers had healed (n = 86). Relative to the adjacent mucosa, 78% of the ulcer margins had increased blood flow (positive delta ISO2) and 22% had decreased blood flow (negative delta ISO2). Stepwise multi-linear regression analysis selected delta ISO2, ulcer size, and stigmata of recent hemorrhage as predictors of delayed healing. A significant negative linear correlation between delta ISO2 and ulcer healing time (r = -0.35, p < 0.001, n = 86) was demonstrated. The scatter in the data precludes prediction of ulcer healing based on delta ISO2 measurement in an individual patient. Multi-variate logistic regression analysis selected concurrent medical illness, duodenal deformity, frequent use of non-steroidal anti-inflammatory drugs, and stigmata of recent hemorrhage as factors significantly associated with delayed (longer than 5 weeks) ulcer healing. The results support the hypothesis that prognostic factors are identifiable at the time of ulcer diagnosis, even in patients who present with bleeding. Blood flow remains an equivocal factor that deserves to be re-studied taking multiple measurements around the ulcer and including a larger number of slow healers.