Objective: While the new DSM-5 anxious distress specifier is of great clinical importance, no evidence exists for its longitudinal predictive validity for clinical outcomes in patients with major depressive disorder (MDD). We examined the longitudinal validity of this specifier and validated it against DSM-IV-based comorbid anxiety disorder diagnoses. Methods: Data are from 1,080 patients with current MDD at baseline (September 2004 to February 2007), of which 911 participated in the 2-year follow-up (September 2006 to April 2009). Patients are from the Netherlands Study of Depression and Anxiety, which is an ongoing longitudinal cohort study, and were sampled from the community, primary care, and outpatient specialized care settings. The specifier was constructed in the existing sample by 5 matching self-report items. Predictive outcomes were 2-year chronicity, time to remission of MDD, and functional disability. Discriminant performance and convergent validity of the specifier were also assessed. Results: The specifier was present in 54.2% of the sample. The specifier significantly outperformed anxiety disorders in predicting chronicity (OR = 1.96, P <.001, vs OR = 1.11, P =.49), time to remission of MDD (HR = 0.75, P =.002, vs HR = 0.94, P =.55), and functional disability (B = 10.03, P <.001, vs B = 2.53, P =.07). The specifier significantly discriminated in clinical characteristics, had convergent validity for anxiety characteristics, and poorly overlapped with DSM-IV-based anxiety disorder diagnoses (Cohen ϵ =.09). Conclusions: The short anxious distress specifier outperforms DSM-IV-based anxiety disorder diagnoses as a longitudinal predictor for clinical outcomes in patients with MDD.