Objective: This study investigates the relationship between antidepressant response to escitalopram and polymorphism of the serotonin transporter gene promoter region (5-HTTLPR) in multi ethnic Malaysian patients with Major Depressive Disorder. Methods: An eight weeks prospective study of treatment response to escitalopram was conducted on 29 Malaysian patients with Major Depressive Disorder. The severity and improvement of depression were assessed with the Montgomery-Asberg Depression Rating Scale. Patients were also genotyped for long (L) and short (S) polymorphisms in 5-HTTLPR using polymerase chain reaction. Results: Response to escitalopram treatment was more frequent in patients with 5-HTTLPR SS genotype than in those with LL or LS genotypes (p = 0.04, OR = 10.0, 95% CI = 1.05-95.2). The favourable allelic variant for response was S allele (p