Objective: To evaluate effects of the MINDSTRONG© cognitive-behavioral skills building program versus an attention control program on mental health outcomes and lifestyle behaviors of graduate health professional students. Participants: 201 entering graduate students from seven health sciences colleges at a public land grant University in the U.S. Midwest. Methods: A randomized controlled trial was conducted with three-month follow-up. Valid and reliable instruments measured depression, anxiety, stress, healthy lifestyle beliefs and healthy lifestyle behaviors. Results: Students receiving MINDSTRONG© reported less depression/anxiety and healthier lifestyle behaviors than those receiving the control program. Students with elevated levels of depression/anxiety at baseline demonstrated greater benefits from the program. Conclusions: MINDSTRONG© can be used as a preventive and early intervention for improving mental health outcomes and lifestyle behaviors in graduate students. Because the program can be delivered by trained non-mental health professionals, it has the potential to be widely scaled on campuses throughout the U.S.