While there is some preliminary evidence that the tryptophan hydroxylase I (TPH1) polymorphisms are related to Borderline Personality Disorder (BPD), it is not clear if this association is due to the high rates of suicidal behavior in this patient group. Because of the reported association between TPH1 polymorphisms and suicidal behavior, determining whether TPH1 is related to BPD independent of suicidal behavior is of particular importance. One hundred patients diagnosed with BPD and 101 healthy controls were genotyped for TPH1 intron 7 A218C polymorphism and assessed for impulsiveness and hostility. The BPD patient group had a higher frequency of A allele carriers (AA/AC genotypes) than the control group (χ2 = 6.12, df = 1, P = 0.01), and differed by genotype frequencies (P = 0.03). Suicide attempter status in the patient group was not related to genotype. Logistic regression analysis controlling for age and gender predicted BPD diagnosis from TPH1 allele group (AA/AC vs. CC, P = 0.03), and TPH1 heterozygotes (AC) appeared to have the highest risk for BPD (P = 0.03). In the full sample, participants with the AC genotype had higher impulsiveness and hostility scores. However, TPH1 did not predict these traits in either of the groups independently, suggesting the association may be an artifact of the association between TPH1 and BPD. Results suggest that the A allele of the tryptophan hydroxylase-1 A218 polymorphism may be associated with BPD, and that it does not appear to be related to suicidal behavior in this population. An aspect of BPD pathology may be due to serotonergic dysfunction. © 2008 Wiley-Liss, Inc.