Objective: Thus far, most applications in precision mental health have not been evaluated prospectively. This article presents the results of a prospective randomized-controlled trial investigating the effects of a digital decision support and feedback system, which includes two components of patient-specific recommendations: (a) a clinical strategy recommendation and (b) adaptive recommendations for patients at risk for treatment failure. Method: Therapist-patient dyads (N = 538) in a cognitive behavioral therapy outpatient clinic were randomized to either having access to a decision support system (intervention group; n = 335) or not (treatment as usual; n = 203). First, treatment strategy recommendations (problem-solving, motivation-oriented, or a mix of both strategies) for the first 10 sessions were evaluated. Second, the effect of psychometric feedback enhanced with clinical problem-solving tools on treatment outcome was investigated. Results: The prospective evaluation showed a differential effect size of about 0.3 when therapists followed the recommended treatment strategy in the first 10 sessions. Moreover, the linear mixed models revealed therapist symptom awareness and therapist attitude and confidence as significant predictors of an outcome as well as therapist-rated usefulness of feedback as a significant moderator of the feedback-outcome and the not on track-outcome associations. However, no main effects were found for feedback. Conclusions: The results demonstrate the importance of prospective studies and the high-quality implementation of digital decision support tools in clinical practice. Therapists seem to be able to learn from such systems and incorporate them into their clinical practice to enhance patient outcomes, but only when implementation is successful. What is the public health significance of this article? This randomized clinical implementation trial provides insight into the evaluation of a clinical decision support and feedback system including personalized pretherapy recommendations and enhanced psychometric feedback during treatment. As it is one of the first decision systems to have been implemented and evaluated prospectively in mental health, this study helps to improve such systems designed to support and change the way psychotherapy is conducted. The results underscore the importance of high-quality implementation of digital decision support tools in clinical practice.