Whether the acute outcomes of major depressive disorder (MDD) treated in primary (PC) or specialty care (SC) settings are different is unknown. To compare the treatment and outcomes for depressed outpatients treated in primary versus specialty settings with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a broadly inclusive effectiveness trial. Open clinical trial with citalopram for up to 14 weeks at 18 primary and 23 specialty sites. Participants received measurement-based care with 5 recommended treatment visits, manualized pharmacotherapy, ongoing support and guidance by a clinical research coordinator, the use of structured evaluation of depressive symptoms and side effects at each visit, and a centralized treatment monitoring and feedback system. A total of 2,876 previously established outpatients in primary (n = 1091) or specialty (n = 1785) with nonpsychotic depression who had at least 1 post-baseline measure. Remission (Hamilton Depression Rating Scale for Depression [Hamilton] or 16-item Quick Inventory of Depressive Symptomatology-Self-Rated [QIDS-SR(16)]); response (QIDS-SR(16)); time to first remission (QIDS-SR(16)). Remission rates by Hamilton (26.6% PC vs 28.0% SC, p = .40) and by QIDS-SR(16) (32.5% PC vs 33.1% SC, p = .78) and response rates by QIDS-SR(16) (45.7% PC vs 47.6% SC, p = .33) were not different. For those who reached remission or response at exit, the time to remission (6.2 weeks PC vs 6.9 weeks SC, p = .12) and to response (5.5 weeks PC vs 5.4 weeks SC, p = .97) did not differ by setting. Identical remission and response rates can be achieved in primary and specialty settings when identical care is provided.