BACKGROUND: Limb reduction deficiencies that are accompanied by amniotic bands (AB-Ls) and terminal transverse limb deficiencies (TLDs) have each been attributed to vascular disruption; for the former, however, it is not clear if amniotic bands are the primary cause of or are secondary to vascular disruption. If amniotic bands are secondary to vascular disruption, then a shared pathogenesis for each case group might be exhibited by similar risk factors. METHODS: We evaluated maternal age, education, race/ethnicity, parity, pregnancy wantedness, and vasoactive exposures among 139 AB-L and 373 TLD cases, using interview data collected from mothers in 10 states by the National Birth Defects Prevention Study. Vasoactive exposures included maternal cigarette smoking and use of decongestants, nonsteroid anti-inflammatory drugs, and antihypertensive drugs in the periconceptional period. RESULTS: Increased risk estimates were observed for Black mothers (OR 2.5; 95% CI: 1.5–4.1) and nulliparous mothers (2.1; 1.4–3.0) in relation to AB-L, while neither was associated with TLD. Hispanic women (1.4; 1.0–1.9) and those not wanting the pregnancy (1.5; 1.1–2.1) had increased risks of TLD, but not AB-L. Maternal cigarette smoking and aspirin use each increased the risk of AB-L, but not TLD; while decongestants and possibly antihypertensive medications increased the risk of TLD, but not AB-L. CONCLUSIONS: The lack of consistent findings for the two case groups suggests that AB-L and TLD may be distinct entities. The inconsistencies also suggest that these vasoactive exposures may not be markers for vascular disruption or that vascular disruption may not play a major role in the pathogenesis of these two types of limb deficiencies. Birth Defects Research (Part A), 2009. © 2008 Wiley-Liss, Inc.