OBJECTIVE: This secondary data analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared clinical characteristics and outcome after citalopram treatment for Hispanic outpatients whose language preference was English (N=121) or Spanish (N=74). METHODS: Data for Hispanic outpatients with nonpsychotic major depression were gathered from two STAR*D regional centers. Participants received citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission with a measurement-based care approach, with adjustments symptoms and side effects. RESULTS: Spanish speakers were older, were more likely to be women, were less educated, had lower income, had more medical burden, and were more likely than English speakers to be seen in primary care rather than in psychiatric clinics. Compared with Spanish speakers, English speakers had more previous suicide attempts and more family history of mood disorders. The groups did not differ in a clinically meaningful way in severity of depression. Before adjustment for baseline differences, Spanish-speaking participants had lower rates of and slower times to remission and response compared with English speakers. After adjustment for baseline variables, these differences were no longer significant. Relapse rates did not differ between groups. CONCLUSIONS: Compared with English-speaking Hispanic patients, Spanish-speaking Hispanic patients may have a less robust response to antidepressants. The reasons for this are not clear but may include more disadvantaged social status. The degree to which these results can be generalized to other Hispanic populations or to other non-English-speaking groups remains to be seen.