OBJECTIVES: To investigate the clinical profiles, modification of therapeutic strategies, relapse rate and resource utilization in patients with schizophrenia who are at risk of non-adherence to oral antipsychotic (AP) medication. METHODS: A Spanish cohort of 596 outpatients with schizophrenia whose therapy was modified because of risk of non-adherence to oral AP medication was followed during 12 months. Baseline and 6-month data on sociodemographic and clinical characteristics, as well as on resource utilization are described. RESULTS: Patients’ mean (SD) age was 40.1 (11.1) years, and 64% were males. The median (IQR) time-since-diagnosis was 14 (15) years. Within the prior 6 months, 124 (21%) had been hospitalized at least once with mean duration of 26 days. Patients had severe symptoms (CGI-S mean score of 4.3), poor quality of life (mean EuroQol-5D health-status value of 0.6) and functional status (mean SOFAS score of 50.6). Baseline non-pharmacologic therapies were modified in 189 (32%) patients, AP medication in 503 (85%) and concomitant medication in 15% . Modifications of AP medications were mostly dose adjustments (64%). Depot formulation was started by 15%. After 6 months, 65 patients (11%) relapsed. These had worse CGI-S and SOFAS scores than patients who did not relapse (4.2 and 51.4 versus 3.7 and 58.6, respectively), whilst EuroQol-5D scores were similar (0.7 in both groups). Hospitalization was required by 35 out of 65 (53.9%) patients who relapsed (38.7 days on average), but just by 5 out of 531 (0.9%) of those who did not relapse (5.4 days on average). Visits to emergency room occurred, respectively, in 44 out of 65 (67.7%) and in 74 out of 531 patients (14%) . CONCLUSIONS: After baseline treatment modification the proportion of patients requiring hospitalizations within 6 months was reduced. Patients who relapsed consumed more resources.