To further control for shared genetic and environmental risks for suicide, we evaluated twin pairs doubly discordant for smoking and suicide by ascertaining twin pairs in which one twin died by suicide whereas the co-twin was alive in 2011 or had died from another cause, in which smoking status was known for both co-twins in 1975, and in which one twin was an active smoker in 1975 while the co-twin was a never smoker. In all, 28 twin pairs were doubly discordant (eight MZ, 18 DZ, two uncertain zygosity). Of these, the twin who committed suicide was an active smoker in 24 pairs (seven MZ, 15 DZ, two uncertain zygosity), and the never-smoking twin was alive or died from another cause, while the converse was true for four pairs [overall OR 6 (24/4), 95% CI 2.1–23.8; OR 7 for MZ pairs, McNemar p = 0.034; OR 5 for DZ pairs, p < 0.005]. A test for homogeneity of ORs across zygosity groups indicated no difference by zygosity (p = 0.80). Likewise, the risk estimates did not differ by sex (men OR 5.67, women OR 7.00, p = 0.86).