To address implementation challenges faced by some evidence-based youth psychotherapies, we developed an efficient transdiagnostic approach-a potential "first course" in evidence-based treatment (EBP)-guided by five empirically supported principles of therapeutic change. An open trial of the resulting FIRST protocol was conducted in community clinics. Following a 2-day training, staff practitioners treated 24 clinically referred youths ages 7-15, 50% male, 87% White and 13% Latino, all with the Schedule for Affective Disorders and Schizophrenia for School-Age Children Diagnostic and Statistical Manual of Mental Disorders (4th ed.) anxiety, depressive, or conduct-related disorders, and averaging 2.21 disorders. We evaluated the protocol's (a) feasibility for use in everyday clinical practice (examining therapy process, client engagement, and therapist adherence and competence in using the protocol), (b) acceptability (examining therapeutic alliance and treatment satisfaction by youths, caregivers, and therapists), and (c) potential for clinical benefit (examining treatment outcomes across multiple measures and time points). FIRST scored well on measures of feasibility, acceptability to clients and clinicians, and clinical outcomes, matching or exceeding the corresponding scores in most benchmarking comparisons. Observational coding of sessions showed high levels of protocol adherence (86.6%) and good therapist competence in the evidence-based skills. Weekly assessments throughout treatment showed effect sizes for clinical improvement ranging from .41 to 2.66 on weekly total problems and problems deemed "most important" by caregivers and youths. The FIRST protocol showed evidence of feasibility, acceptability, and clinical benefit when used by practitioners with referred youths treated in community clinics. The findings suggest sufficient potential to justify a full randomized controlled trial of FIRST.