OBJECTIVE: To determine whether completing a mindfulness-based stress reduction (MBSR) program would affect the general health, health-related quality of life, sleep quality, and family harmony of Spanish- and English-speaking medical patients at an inner-city health center. MATERIALS AND METHODS: An intervention group of 68 patients (48 Spanish-speaking and 20 English-speaking) completed the SF-36 Health Survey and two additional questions about sleep quality and family harmony before and after completing the 8-week MBSR program. A comparison group of 18 Spanish-speaking patients who received no intervention completed the same questionnaire at the same intervals. RESULTS: Sixty-six percent of the total intervention group completed the 8-week MBSR program. There was significant comorbidity of medical and mental health diagnoses among the intervention and comparison groups, with no differences in the mean number of diagnoses of the total intervention group, the comparison group, or the Spanish- or English-speaking intervention subgroups. Compared with the comparison group, the intervention group showed statistically significant improvement on five of the eight SF-36 measures, and no improvement on the sleep quality or family harmony items. CONCLUSIONS: MBSR may be an effective behavioral medicine program for Spanish- and English-speaking inner-city medical patients. Suggestions are given for future research to help clarify the program’s effectiveness for this population.