Objective: To examine the effectiveness of an Internet intervention for depression with a randomized, controlled trial in a large sample of adults recruited from the United States. Method: The current study examines the effectiveness of Deprexis, an Internet treatment for depression that was provided with relatively minimal support. There were 376 treatment-seeking adults (mean age = 32 years; 74% female; 77% Caucasian, 7% Asian, 7% multiple races, 4% African American, and 11% Hispanic/Latino) with elevated depression (Quick Inventory of Depressive Symptoms-Self-Report [QIDS-SR] > = 10) who were randomized to receive an 8-week course of treatment immediately (n = 285) or after an 8-week delay (n = 91; i.e., waitlist control). Results: Intention-to-treat analyses indicated that treatment was associated with greater reduction in self-reported symptoms of depression (effect size d = .80) and 12 times greater likelihood of experiencing at least 50% symptom improvement compared with waitlist control. Similar effects were observed for several secondary outcomes, such as interviewer-rated depression symptoms, well-being, and depression-related disability. Treatment effects for symptoms of social anxiety, panic, and traumatic intrusions were relatively small. Conclusion: Results suggest that Deprexis can produce symptomatic improvement among depressed adults recruited from the United States. Additional research is needed that examines whether improvements are maintained over time and who is particularly likely to respond to this form of treatment.