The relationship between depression following traumatic brain injury (TBI), antidepressant treatment response and short (s) or long (l) alleles of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism was examined. Of 156 mild-to-moderate TBI patients (96M, 50F; 34.4+/-16.9 years; 5-HTTLPR: 27.4% s/s, 50.7% s/l, or 21.9% l/l), depressed (n=34) and non-depressed (n=112) were similar in genotype frequencies (p>.05). While responders (n=5) and non-responders (n=14) to citalopram treatment (20 mg/day for 6 weeks) did not differ in genotype frequencies (p>.05), the s/s group had a smaller response compared to the l-allele carriers (HAMD change s/s: -4.9+/-6.5 vs. s/l & l/l: -9.5+/-4.9; p=.097). Neuroticism (p=.001), low extrovertness (p=.024), and post-concussion somatic symptoms (p<.001) were strong predictors of depression chi2=71.0, p<.001). These results suggest that the 5-HTTLPR polymorphism does not strongly influence risk of depression post-TBI, but the s/s genotype may be associated with poorer citalopram response.