The study prospectively examined the economic outcomes and co-medications among first-episode schizophrenic patients treated with monotherapy of second-generation antipsychotic agents (SGAs) continuously as compared with each other and with haloperidol. The sample included 3047 out of Taiwan's national sample of 29,341 first-episode schizophrenic patients, who were selected, based on International Classification of Disease, Ninth Revision code 295, from the National Health Insurance original claims data from 1999 to 2004. They were treated with only 1 of the following antipsychotic agents: haloperidol (n = 526), clozapine (n = 224), risperidone (n = 827), olanzapine (n = 824), zotepine (n = 286), or quetiapine (n = 360), without changing antipsychotics during the observation for at least 1 year (mean, 1.80 years; SD, 0.93 years) for each subject. Economic outcomes included clinic visits, prescription days, frequencies and duration of hospitalizations, and total and separate treatment costs (outpatient department- and hospital-related costs). Co-medications included use of anticholinergic, anxiolytic, hypnotic/sedative, and antidepressant agents. Patients treated with SGAs had lower number and shorter durations of hospitalizations than did haloperidol-treated patients, except for the clozapine group. Olanzapine was associated with the lowest hospitalization rates per year (mean, 1.63 vs 2.83). In terms of cost, haloperidol was more expensive in total hospitalization expenses (mean, US $3215 per year) and total treatment cost (mean, $3769 per year) than olanzapine, zotepine, or quetiapine. In general, there was no difference among the haloperidol and SGA groups in terms of rates of co-medications. The reduced number of hospitalizations and then lower total hospitalization costs seem to be more than the offset of high medication acquisition costs of SGAs.