BACKGROUND: Aortic dissection (AD) is a challenging diagnosis associated with severe mortality. However, acute AD is a rare clinical entity and can be overevaluated in the emergency department. D-dimer, both alone and in combination with the Aortic Dissection Detection Risk Score (ADD-RS), has been studied as a tool to evaluate for AD. CLINICAL QUESTION: Can a negative D-dimer in low-risk patients exclude AD in the emergency department? EVIDENCE REVIEW: Retrieved studies included three systematic review and meta-analyses and two prospective cohort studies. D-dimer was found to be highly sensitive for acute AD, with a sensitivity of 98.0%. The ADD-RS was also highly sensitive (95.7%) for AD. Two meta-analyses reported a combination of a negative D-dimer and ADD-RS < 1 to have a pooled sensitivity of 99.9% and 100% for acute aortic syndrome. CONCLUSIONS: Neither D-dimer nor the ADD-RS alone provides adequate sensitivity to exclude acute AD. However, a negative D-dimer combined with an ADD-RS < 1 is likely sufficient to rule out AD. Even with these findings, physicians must place clinical judgment above laboratory testing or scoring systems when deciding whether to pursue a diagnosis of acute AD.