Methamphetamine use is associated with numerous harms and consequently represents a significant impact on Australia s treatment and health service sectors. This article presents baseline findings from the first cohort study of regular methamphetamine users conducted in Melbourne, describing associations between participant characteristics and behaviours and methamphetamine dependence. A total of 255 Melbourne-based, regular methamphetamine users were recruited during 2010 and administered a structured questionnaire. Most were male and Australian-born with a median age of 30 years. Sixty percent of the participants were classified as methamphetamine dependent using the Severity of Dependence Scale. The socio-demographic characteristics of these participants were generally comparable to non-methamphetamine-dependent participants; however, methamphetamine dependence was independently associated with experience of high levels of psychological distress during the previous month, current use of prescribed mental health medication and primarily injecting methamphetamine over other routes of administration. Polysubstance use was universal; many participants also reported recent use of cannabis and heroin. Despite the fundamentally different recruitment criteria, the socio-demographic characteristics of the community-recruited baseline sample reflect those of methamphetamine-using samples recruited in other Australian jurisdictions since the mid-1990s. This study provides important up-to-date data on methamphetamine use in Melbourne and is an important basis for understanding any future changes to patterns of methamphetamine use in this region.