In the present study, we report the initiation to the first drug in a representative sample of drug dependents in Iran. This is a cross-sectional study with a sample size of 7,743. The participants were characterized as drug dependents according to the Diagnostic and Statistical Manual-Fourth Edition and were sampled from the medical centers, prisons, and streets of the capitals of 29 provinces in the Islamic Republic of Iran. The mean age at first drug use in the sample was 21.1 (6.5), which differed for various first drugs of abuse. Opium was the first drug of use among 46.4% of the sample, and cannabis was the first drug only among 23.5%. The most frequent place of initiation was at a friend's house (n = 2,476, 33.2%). The same-gender friend out of school (the highest rate) was the most frequent person who suggested the first use. A total of 43.5% of the participants started drug use with friends and 18.8% at a friend's party. Policymakers may benefit from considering the information provided here in designing programs with the purpose of prevention.