Background: Women of childbearing age report high rates of alcohol consumption, which may result in alcohol exposure during early pregnancy. Epidemiological research on congenital limb deficiencies (LDs) and periconceptional exposure to alcohol is inconclusive. Methods: Data from the National Birth Defects Prevention Study (NBDPS) were examined for associations between LDs and patterns of maternal periconceptional (1 month before conception through the first trimester) alcohol consumption among LD case (n = 906) and unaffected control (n = 8352) pregnancies with expected delivery dates from 10/1997 through 12/2007. Adjusted odds ratios (aORs) and 95% confidence intervals were estimated from unconditional logistic regression analysis for all LDs combined, specific LD subtypes (preaxial/terminal transverse), and LD anatomic groups (upper/lower limbs); interactions with folic acid (FA) supplementation were tested. Results: When compared with nondrinkers, inverse associations were found between all LDs combined, preaxial, and upper LDs and any reported periconceptional alcohol consumption (aORs ranged from 0.56–0.83), drinking without binging (aORs: 0.53–0.75), and binge drinking (≥4 drinks/occasion) (aORs: 0.64–0.94); however, none of the binge drinking aORs were statistically significant. Stratification by alcohol type showed inverse associations between all LDs combined, preaxial, transverse, and upper and lower LDs for drinking without binging of wine only (aORs: 0.39–0.67) and between all LDs combined and upper LDs for drinking without binging of combinations of alcohol (aORs: 0.63–0.87). FA did not modify observed associations. Conclusion: Maternal periconceptional alcohol consumption did not emerge as a teratogen for selected LDs in the NBDPS. Future studies should evaluate additional rare LDs among more highly exposed populations. Birth Defects Research (Part A) 100:863–876, 2014. © 2014 Wiley Periodicals, Inc.