This study investigates the effectiveness of short-term psychodynamic psychotherapy (STPP) for depression in a naturalistic setting utilizing a hybrid effectiveness/efficacy treatment research model. Twenty-one patients were assessed pre- and post-treatment through clinician ratings and patient self-report on scales representing specific DSM-IV depressive, global symptomatology, relational, social, and occupational functioning. Treatment credibility, fidelity, and satisfaction were examined, all of which were found to be high. All areas of functioning assessed exhibited significant and positive changes. These adaptive changes in functioning demonstrated large statistical effects. Likewise, changes in depressive symptoms evaluated at the patient level utilizing clinical significance methodology were found to be high. A significant direct process/outcome link between STPP therapist techniques and changes in depressive symptoms was observed. Alternative treatment interventions within STPP were evaluated in relation to subsequent improvements in depression and were found to be nonsignificant. The present results demonstrate that robust statistical and clinically significant improvement can occur in a naturalistic/hybrid model of outpatient STPP for depression.