Objective: The authors compared measurement-based care with standard treatment in major depression. Methods: Outpatients with moderate to severe major depression were consecutively randomized to 24 weeks of either measurement-based care (guideline- and rating scalebased decisions; N=61), or standard treatment (clinicians? choice decisions; N=59). Pharmacotherapy was restricted to paroxetine (20?60mg/day) or mirtazapine (15?45mg/day) in both groups. Depressive symptoms were measured with the Hamilton Depression Rating Scale (HAM-D) and the Quick InventoryofDepressiveSymptomatology? Self-Report (QIDS-SR). Time to response (a decrease of at least 50% in HAM-Dscore) and remission (a HAM-D score of 7 or less) were the primary endpoints. Outcomes were evaluated by raters blind to study protocol and treatment. Results: Significantly more patients in the measurementbased care group than in the standard treatment group achieved response (86.9% compared with 62.7%) and remission (73.8% compared with 28.8%). Similarly, time to response and remission were significantly shorter with measurement-based care (for response, 5.6 weeks compared with 11.6 weeks, and for remission, 10.2 weeks comparedwith 19.2weeks).HAM-Dscores decreasedsignificantly in both groups, but the reduction was significantly larger for the measurement-based care group (217.8 compared with 213.6). The measurement-based care group had significantlymoretreatment adjustments (44comparedwith 23) and higher antidepressant dosages from week 2 to week 24. Rates of study discontinuation, adverse effects, and concomitant medications did not differ between groups. Conclusions: The results demonstrate the feasibility and effectiveness of measurement-based care for outpatients with moderate to severe major depression, suggesting that this approach can be incorporated in the clinical care of patients with major depression.