We investigated the clinical efficacy of mirtazapine in Chinese patients with major depressive disorder (MDD) and also examined mirtazapine's effects on the serum brain-derived neurotrophic factor (BDNF) levels in these patients. Fifty-eight geriatric patients with major depression were assigned to an 8-week treatment with either 15 to 45 mg/day of mirtazapine. The efficacy measurements were performed by the Clinical Global Impression rating scales (CGI). Serum BDNF levels were measured using enzyme-linked immunosorbent assay (ELISA). In the study, mean serum BDNF level of untreated depressed patients at baseline was 23.08 ± 11.25 ng/ml and the mean Hamilton Rating Scale for Depression (HRSD) score was 27.8 ± 5.4. After remission was achieved, the mean serum BDNF level was 37.15±20.48 ng/ml whereas the mean HRSD score was 9.6±4.1. After 8 weeks of treatment there was a statistically significant difference in the serum BDNF levels. Meanwhile, HRSD scores and CGI scores were decreased significantly after mirtazapine treatment. Whatever male or female patients, mirtazapine significantly improved serum BDNF levels and decreased the CGI and HRSD scores from baseline. The results showed serum BDNF levels may be considered as a marker of response to mirtazapine antidepressant treatment for Chinese geriatric patients with major depression. And mirtazapine has been an important option for the treatment of major depression in geriatric patients.