Previous research has shown that interpersonal conflict and depression are cross-sectionally associated with hostility. Our objective was to determine whether hostility is longitudinally predictive of interpersonal distress and depression and to replicate previous research that suggests that hostility is a risk factor for other health behaviors (e.g., smoking and excessive alcohol use) and psychosocial health problems. We use data from the youngest generation of a three-generation, 11-year follow-up study of Mexican Americans, that represent 251 Mexican Americans between the ages of 18 and 42 years. Our indicator of hostility was the irritability subscale from the Buss-Durkee Hostility Inventory. After statistically controlling for marital status, language acculturation, education, age, and sex, irritability was found to predict subsequent heavy drinking, somatic symptoms associated with depression, psychosomatic symptoms, infectious disease, divorce, marital separation, ending a serious nonmarital relationship, not being married at the follow-up, and more negative feelings associated with divorce, marital separation, and ending a serious relationship. Our research supports theory and research suggesting that hostility is predictive of physical symptoms, poor health habits, and interpersonal conflict.