This research investigated whether chronic strain and self-esteem can significantly predict substance use problems. Chronic strain in this study is defined by various stressful life events. The literature stated that higher self-esteem has been associated with avoidance and reduced substance use (Carvajal et al., 1998; Emery et al., 1993). Chronic substance use was associated with psychological strain (Preston, 2006). To look further into these relationships, the data from Project STRIDE: Stress, Identity, and Mental Health, New York City, 2004-2005 (Meyer et al., 2004-2005) were used. There was a total of 524 participants ranging in ages from 18 to 58 and located in New York City. A logistic regression approach was used to answer the research question. The preliminary analysis showed that the assumption of linearity of the logit was met, and no multicollinearity was detected. The analysis results showed that there was a 6 percent significant improvement in prediction of substance use problems with chronic strain and self-esteem, X2(2) = 16.07, p < .05, with 87.6 percent correct classification. Cox and Snell R2 was .06 and Nigelkerke R2 was .11. The odds of an individual with high self-esteem not having a substance use problem are 3.72 times higher than an individual with a low self-esteem. Chronic strain, however, did not significantly predict the probability of having a substance use problem.