Instruments for the initial evaluation of emergency room patients as an aid to their onward referral to ambulatory care structures are a matter of current interest. In this study, we assess the safety of the software application SmED-Kontakt+ for this purpose. SmED is an abbreviation for Strukuturierte Medizinische Ersteinschätzung Deutschland, "structured initial medical evaluation in Germany." In this prospective cohort study, we compared the recommendations of SmED-Kontakt+ concerning the time and place of further care with those of the treating physicians. The subjects were adult patients who were able to walk and had presented themselves to the emergency room. Whenever SmED-Kontakt+ assessed the situation less critically than the physicians, and in 5% of the remaining cases, the potential endangerment of patient safety was assessed by an expert panel (expected value <1%). In a total of 1840 cases, SmED-Kontakt+ agreed with the physicians' assessment in 353 (19%). The assessment of SmED-Kontakt+ was more critical in 1221 cases (66%) and less critical in 266 (15%; potential undertriage). There was potential endangerment in 49 cases (2.7%; 95% confidence interval [2.0; 3.5]). Potential endangerment was less common among patients in the more urgent recommendation categories [0.1; 2.6] and more common in the categories of a recommended outpatient physician visit or telephone consultation within or beyond 24 hours [2.4; 17.2]. SmED-Kontakt+ generally assessed these patients' needs for further care as more urgent than the treating physicians did. Nevertheless, the percentage of potentially endangered patients was higher than expected. We conclude that further care should be provided in timely fashion with an obligatory appointment. The sites of further ambulatory care should be immediately accessible and properly equipped. Patients should not be referred for further care at later times on the basis of an SmED-Kontakt+ assessment.