Background: Initiation of antidepressant treatment for depression may be associated with new onset (emergent) anxiety. Objective: The purpose of this study was to assess demographic and clinical factors associated with emergent anxiety following a new antidepressant start among Department of Veterans Affairs (VA) Health System patients with depression. Methods: Using a retrospective cohort design, we obtained data from 328,888 VA patients with depression who were newly prescribed 1 of the 7 most commonly used antidepressant drugs between April 1999 and September 2004 from the VA National Depression Registry. We examined the prevalence of emergent anxiety, defined as either a new anxiety diagnoses or by new antianxiety medication starts, during the 12 weeks following new antidepressant start. In multivariate analyses, we assessed the hazard ratios for emerging anxiety associated with patient characteristics and specific antidepressant agents. Results: Approximately 3% of patients developed clinically significant anxiety within 12 weeks of starting an antidepressant drug regimen. Younger age (age = years) (hazard ratio [HR] = 1.72 and 1.55; 95% CI, 1.59-1.85, and 1.38-1.72, respectively). Female gender was associated with higher risks than male gender (HR = 1.17; 95% CI, 1.10-1.26), and white and other races compared with black race were associated with higher risks of emergent anxiety (HR = 1.49 and 1.13; 95% CI, 1.30-1.59 and 1.04-1.23, respectively). Finally, filling antidepressant drug prescriptions in years subsequent to 1999 was associated with lower risks of emergent anxiety. Conclusions: Only a small proportion of patients developed emergent anxiety following a new antidepressant start, resulting in a new diagnosis or antianxiety medication use. Anxiety occurred more often in young adults, whites, and women. (Clin Ther. 2011; 33:1985-1992) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.