Objective: Anxiety and depression are prevalent among medical students. Brazilian medical students have higher levels of depression and lower quality of life than their U.S. counterparts, and no preventive intervention exists for this risk group in Brazil. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP), a cognitive-behavioral treatment protocol for neuroticism, was recently adapted into a single-session, preventive intervention. This study tested the impact of this protocol on psychiatric symptoms and quality of life in Brazilian medical students. Methods: In this open trial, the intervention protocol was translated and adapted to Brazilian Portuguese. Medical students over 18 years of age without psychotic symptoms, severe depressive episodes, or acute psychiatric risk were included, undergoing a psychiatric clinical interview (Mini-International Neuropsychiatric Interview [MINI]) and evaluation at baseline and at 7 and 30 days after a single-session UP that included experimental avoidance, quality of life, self-esteem, empathy, and anxiety symptom scales. A new evaluation was performed 90 days after the intervention. Results: Sixty-two students participated. Ninety days after the intervention, there were significant reductions in the number of students who met the criteria for social anxiety disorder (p = 0.013) or panic disorder (p = 0.001). There were also significant improvements in depressive symptoms (Beck Depression Inventory, p o 0.001) and quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire, p o 0.001). Conclusion: UP improved anxiety and depressive symptoms in medical students. The single-session group format could reduce costs and facilitate application. Future placebo-controlled studies are necessary to confirm these findings.