Poor adherence limits the effectiveness of antipsychotic treatment in people with psychosis. The aim of the pragmatic, exploratory, single-masked trial conducted in the USA was to explore the efficacy, acceptability, and satisfaction with adherence therapy (AT) in a sample of people with schizophrenia. Twenty-six patients (12 experimental and 14 controls) were randomly allocated to receive eight weekly sessions of AT or continue with their treatment as usual (TAU). Patients were assessed at baseline and follow up (after therapy completion). The primary outcome was psychiatric symptoms, assessed using the Positive and Negative Syndrome Scale (PANSS). The secondary outcome, medication adherence, was measured by The Personal Evaluation of Transitions in Treatment. Patients receiving AT did not significantly improve in overall psychiatric symptomatology (change in PANSS total scores: AT: -10.2, TAU: -8.6; mean difference, -1.6; P = ns) or with medication adherence (AT: -2.8, TAU 1.5; P = ns) compared with the TAU group at follow up. Using the Adherence Therapy Patient Satisfaction Questionnaire, a high degree of satisfaction with AT was reported. Although AT did not result in a statistically-significant improvement in symptoms or medication adherence, evidence of active clinical engagement in treatment occurred.