BACKGROUND: The optimum management of isolated penetrating aortic ulceration (PAU), with no associated intramural hematoma or aortic dissection is not clear. We evaluate the short- and long-term outcomes in isolated PAU to better inform management strategies. METHODS: We conducted a retrospective review of 43 consecutive patients (mean age, 72.2 years; 26 men) with isolated PAU (excluding intramural hematoma/aortic dissection) managed at a single tertiary vascular unit between November 2007 and April 2019. Twenty-one percent had PAU of the arch, 62% of the thoracic aorta, and 17% of the abdominal aorta. Conservative and surgical groups were analyzed separately. Primary outcomes included mortality, PAU progression, and interventional complications. RESULTS: Initially, 67% of patients (29/43) were managed conservatively; they had significantly smaller PAU neck widths (P = .04), PAU depths (P = .004), and lower rates of associated aneurysmal change (P = .004) compared with those initially requiring surgery. Four patients (4/29) initially managed conservatively eventually required surgical management at a mean time interval of 49.75 months (range, 9.03-104.33 months) primarily owing to aneurysmal degeneration. Initially, 33% of patients (14/43) underwent surgical management; 7 of the 14 procedures were urgent. Of the 18 patients, 17 eventually managed with surgical intervention had an endovascular repair; 2 of the 17 endovascular cases involved supra-aortic debranching, six used scalloped, fenestrated, or chimney stents. The overall long-term mortality was 30% (mean follow-up, 48 months; range, 0-136 months) with no significant difference between the conservatively and surgically managed groups (P = .98). No aortic-related deaths were documented during follow-up in those managed conservatively. There was no in-hospital mortality after surgical repair. Of these 18 patients, two required reintervention within 30 days for type I or III endoleaks. Among the 18 patients, seven died during follow-up (mean survival, 90.24 months; range, 66.48-113.88) with 1 of the 18 having a confirmed aortic-related death. CONCLUSIONS: Isolated, asymptomatic, small PAUs may be safely managed conservatively with regular surveillance. Those with high-risk features or aneurysmal progression require complex strategies for successful treatment with acceptable long-term survival.