While the United States hosts the greatest number of international students in the world, Latino international students remain understudied, especially in regards to substance use. The present study tests differences between Latino international and Latino domestic undergraduates in how they use alcohol, cigarette, and illicit drugs. Participants (N = 786 students, 386 international and 400 domestic, 65% female, mean age = 21.2 years) were a subsample of Latino students surveyed in the 2009 American College Health Association's revised National College Health Assessment (ACHA-NCHA II). Results indicate that Latino international students reported more alcohol use than Latino domestic students, but had similar use of cigarettes and illicit drugs. Among international students, gender, participation in Greek life, cigarette use, marijuana use, and year in school were associated with alcohol use. Similarly, gender, cigarette use, and marijuana use were significantly related to international students' binge drinking. Prevention and research implications are discussed.