More than 20 years ago Habib Davanloo coined the term unlocking of the unconscious to describe how the psychodynamic concept of the human unconscious can become accessible using the technique of Intensive Short-Term Dynamic Psychotherapy (ISTDP). According to Davanloo, the possibility that unconscious material will be revealed is greatly increased when therapeutic efforts promote dominance of the unconscious therapeutic alliance over unconscious resistance. When these ingredients are present there is a psychic shift that allows unacceptable painful feelings to come to the surface. Toward adding further empirical support for the concept, in this article we compare outcomes between patients who experienced one or more major unlocking of the unconscious (N = 57) to those who did not experience major unlocking (N = 32) during ISTDP treatment. Significant and widespread differences were seen between these two groups, those with major unlocking had greater symptom reduction, interpersonal gains, and cost reduction for treatment. The relevance of this to clinical practice and healthcare utilization will be discussed.