Introduction: Depression and anxiety are common affective experiences during the first year following a solid organ transplant. This study examined the degree to which an evidenced-based clinical intervention implemented by social workers—Symptom Targeted Intervention—can alter self-reported depression and anxiety in heart, kidney, liver, and lung transplant recipients. Research Questions: This investigation explored 2 questions: (1) Can symptom-targeted interventions significantly reduce posttransplant recipients’ self-reported depression and anxiety at the conclusion of treatment and at 1-month follow-up? and (2) Does the response differ by gender? Design: A 1-group pretest–posttest design with a 1-month follow-up was used to test for changes in anxiety and depression after transplantation. Forty-eight patients at 2 US transplant centers were enrolled between January 2016 and May 2017. Data were collected using an online platform and analyzed to assess for differences over time and by gender. Results: Anxiety decreased significantly between pretest and posttest using the General Anxiety Disorder-2 ( P < .05). Comparisons by gender indicated that women had a significant decrease in anxiety between pretest and posttest ( P < .001); however, there was no significant decrease in anxiety for men. Analyses by gender and time yielded no significant differences for depression. Discussion: Symptom-targeted interventions have the potential to reduce anxiety in solid organ transplant patients and enhance their psychosocial adjustment after surgery.