This study examines patterns of substance use among youth served in systems of care, and how these patterns relate to diagnosis and other youth characteristics using latent class analysis. Results indicated a four-class solution with the four groups differing in their probabilities of reporting the use of 10 different substances. Class 1 was defined by high probabilities of all drug use. Class 2 had high probabilities of alcohol, tobacco, marijuana use, and low for other drugs. Class 3 had moderate probabilities of alcohol, tobacco, marijuana use, and low probabilities for other drugs. Class 4 had a high probability of tobacco use and no other drug use. Youth who had a mood disorder diagnosis, were male, older, White and had previously run away from home were significantly more likely to be in Class 1 relative to other classes. These differences have implications for prevention and treatment.