BACKGROUND: Primary care practices in underserved and/or rural areas have limited access to mental health specialty resources for their patients. Telemedicine can help address this issue, but little is known about how patients and clinicians experience telemental health care. METHODS: This pragmatic randomized effectiveness trial compared telepsychiatry collaborative care, where telepsychiatrists provided consultation to primary care teams, to a referral approach, where telepsychiatrists and telepsychologists assumed responsibility for treatment. Twelve Federally Qualified Health Centers in rural and/or underserved areas in 3 states participated. RESULTS: Patients and clinicians reported that both interventions alleviated barriers to accessing mental health care, provided quality treatment, and offered improvements over usual care. Telepsychiatry collaborative care was identified as better for patients with difficulty developing trust with new providers. This approach also required more primary care involvement than referral care, creating more opportunities for clinician learning related to mental health diagnosis and treatment. The referral approach was identified as better suited for patients with higher complexity or desiring specific psychotherapies. CONCLUSIONS: Both approaches addressed patient needs and provided access to specialty mental health care. Each approach better aligned with different patients' needs, suggesting that having both approaches available to practices is optimal for supporting patient-centered care.