The NHSDA is the only study that produces estimates of drug use among members of the household population the United States. The survey is appropriate for estimating prevalence rates for different drugs, since much drug use would not ordinarily come to the attention of administrative, medical, or correctional authorities and therefore would not be included in official statistics. In-person interviews with a large national probability sample seem to be the best way to estimate drug use in virtually the entire population of the United States. Topics covered in the 1991 NHSDA include tobacco, alcohol, and illicit drug use; consequences of various drugs; health condition; treatment for drug use; illegal activities; and use of anabolic steroids. Also, sets of questions regarding insurance and personal and family income sources and amounts were expanded in comparison to previous surveys. The 1991 survey includes 1,283 variables.

The content of the NHSDA changes slightly from year to year. Changes made over the course of the 1990 and 1991 surveys include changes regarding sampling methods, sample populations, and the deletion and addition of variables. The 1991 NHSDA is the first NHSDA to sample from Alaska and Hawaii in addition to the contiguous states. Furthermore, unlike previous surveys, residents of non-institutional group quarters (e.g., college dormitories, group homes, civilians dwelling on military installations) and persons with no permanent residence (homeless people and residents of single rooms in hotels) were sampled in the 1991 NHSDA.