Background: Physicians treating patients in the vegetative state (VS) must deal with uncertainty in diagnosis and prognosis, as well as ethical issues. We examined whether physicians' attitudes toward medical and ethical challenges vary across two national medical practice settings. Methods: A comparative survey was conducted among German and Canadian specialty physicians, based on a case vignette about the VS. Similarities and differences of participants' attitudes toward medical and ethical challenges between the two samples were analyzed with non-parametric tests (Mann-Whitney-U-Test). Results: The overall response rate was 13.4%. Eighty percent of all participants correctly applied the diagnostic category of VS with no significant differences between countries. Many of the participants who chose the correct diagnosis of VS attributed capabilities to the patient, particularly the ability to feel pain (70%), touch (51%) and to experience hunger and thirst (35%). A large majority of participants (94%) considered the limitation of life-sustaining treatment (LST) under certain circumstances, but more Canadian participants were in favor of always limiting LST (32% vs. 12%; Chi-square: p < 0.001). Finding long-term care placement was considered more challenging by Canadian participants whereas discontinuing LST was much more challenging for German participants. Conclusions: Differences were found between two national medical practice settings with respect to physicians' experiences and attitudes about treatment limitation about VS in spite of comparable diagnostic knowledge.