OBJECTIVES: To assess the impact of anxiety and of the depression-anxiety interaction on healthcare utilization and costs among patients with depression. METHODS: Survey-eligible adults with ≥2 medical claims for depression from 6/1/2009-5/31/2010 in the HealthCore Integrated Research Database were invited to participate in this retrospective/prospective study. Consenting respondents completed index and 6-month surveys assessing health measures. Significant anxiety was classified into 4 categories (persistently anxiety free, persistent anxiety, resolving anxiety, and emerging anxiety) based on Generalized Anxiety Disorder (GAD-7) scores at both surveys. Respondents’ survey data were linked to 24-months of claims data (­+12 months from index survey date). Mean annual post-index costs were compared using non-parametric bootstrapping adjusting for initial differences in demographics and health status using propensity score stratification. Similar models were created adding the interaction of remission status. RESULTS: Of 910 respondents with both surveys, 79.3% were female and mean (SD) age was 47.6 (11.4) years. Most respondents were persistently anxiety free (52.9%), followed by persistent anxiety (23.4%), resolving anxiety (15.1%), and emerging anxiety (8.7%). Higher post-index all-cause healthcare costs were observed in respondents with persistent anxiety compared to others (combined group of resolving, emerging, or persistently anxiety-free) ($15,027 [$1,838] vs. $11,311 [$680], p=.0018). Persistent anxiety respondents had significantly higher mental health-related costs than persistently anxiety free respondents ($4,226 [$551] vs. $3,044 [$332], p<.001). Respondents with anxiety and non-remitted depression had significantly higher all-cause and mental-health related costs vs. respondents without anxiety and non-remitted depression, with mean differences of $2,480 (95% CI: $337 to $4,685, p<.0001) and $789 (95% CI: $146 to $1,428, p<.0001), respectively. CONCLUSIONS: Respondents with a history of depression and persistent anxiety continue to have increased healthcare costs. Anxiety was a key factor irrespective of whether depression resolved. This study emphasizes the importance of treating patients to full resolution of all symptoms.