Background: Endoscopic injection is widely used in the therapy of bleeding gastroduodenal ulcers, but its role in the management of bleeding Mallory-Weiss tears has not been properly assessed. Methods: Sixty-three patients undergoing emergency endoscopy in whom there was a high index of suspicion that a Mallory-Weiss tear was the source of bleeding were randomly assigned to undergo endoscopic injection therapy (epinephrine and polidocanol) or no endoscopic therapy in 2 university-affiliated hospitals. Rates of recurrent bleeding, transfusion requirements, complications, mortality, and length of hospital stay were determined for both groups of patients. Results: Bleeding recurred in 8 patients in the control group versus only 2 in the endoscopic treatment group (25.8% vs. 6.2%, p < 0.05). Hospital stay was longer for the control group (5.5 ± 0.2, median 6.0, range 2.0-8.0 days vs. 3.4 ± 0.2, median 3.0, range 2.0-6.0 days; p < 0.001). There was a trend toward a higher transfusion requirement after endoscopy in the control group versus the patients treated by injection (0.9 ± 0.2, median 0.0, range 0.0-4.0 units vs. 0.2 ± 0.1, median 0.0, range 0.0-2.0 units; p = 0.09). No complications or adverse events caused by endoscopic injection were noted. Two patients in the control group died of causes unrelated to bleeding. Conclusions: Endoscopic injection therapy is a useful option in the management of patients with Mallory-Weiss syndrome at high risk for recurrent bleeding. (Gastrointest Endosc 2001;54:679-81.)