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Background: Endoscopic treatment guided by Doppler endoscopic probes (DEPs) during index endoscopy may be associated with improved outcome in patients with peptic ulcer bleeding (PUB). As competencies for DEP evaluation are not always available for index endoscopy, we examined the outcome associated with DEP evaluation at second-look endoscopy. Methods: The study was designed as a non-blinded, parallel group, randomised controlled trial. Patients admitted with PUB from Forrest Ia-IIb ulcers, controlled by endoscopic therapy, were randomised (1:1 ratio) to second-look endoscopy <24 h with DEP evaluation of the bleeding ulcer or continued standard treatment. Patients were followed up for 30 days. The primary outcome was rebleeding. Secondary outcomes included the number of transfusions, length of hospital stay, and 30-day mortality. Results: A total of 62 patients were included. At second-look endoscopy, 91% (29/32) of patients had a positive DEP signal at the ulcer base and were treated with contact thermal therapy (n = 29), injection of diluted adrenaline (n = 23), and haemoclips (n = 7). Among the 32 patients treated with DEP evaluation, only one rebled (3%) compared to four patients (13%) in the control group (p = 0.20). There were no differences in the secondary outcomes between groups, and there were no complications related to DEP evaluation. Conclusions: Second-look endoscopy with DEP-guided evaluation and treatment is safe and associated with a very low risk of rebleeding (3%) in patients with PUB. Second-look endoscopy with DEP evaluation may be considered in selected PUB patients at high risk of rebleeding, and may represent an alternative to the use of DEP for index endoscopy. Nevertheless, we did not find that second-look endoscopy with DEP evaluation significantly improved patient outcome compared to standard treatment. [ABSTRACT FROM AUTHOR]