Introduction: Studies have shown important gender differences among drug (including crack) users related to: drug use patterns; health risks and consequences; criminal involvement; and service needs/use. Crack use is prevalent in Brazil; however, few comparative data by sex exist. We examined and compared by sex key drug use, health, socio-economic indicators and service use in a bi-city sample of young (18–24 years), regular and marginalized crack users in Brazil. Methods: Study participants (total n = 159; n = 124 males and n = 35 females) were recruited by community-based methods from impoverished neighborhoods in Rio de Janeiro and Salvador. Assessments occurred by an anonymous interviewer-administered questionnaire and serum collection for blood-borne virus testing between November 2010 and June 2011. Descriptive statistics and differences for key variables by sex were computed; in addition, a ‘chi-squared automatic interaction detector’ (‘CHAID’) analysis explored potential primary factors differentiating male and female participants. Results: Most participants were non-white, and had low education and multiple income sources. More women had unstable housing and income from sex work and/or panhandling/begging, whereas more men were employed. Both groups indicated multi-year histories of and frequent daily crack use, but virtually no drug injection histories. Men reported more co-use of other drugs. More women were: involved in sex-for-drug exchanges; Blood-Borne Virus (BBV) tested and HIV+. Both groups reported similar physical and mental health patterns; however women more commonly utilized social or health services. The CHAID analysis identified sex work; paid work; begging/panhandling; as well as physical and mental health status (all at p < 0.05) as primary differentiating factors by sex. Conclusions: Crack users in our study showed notable differences by sex, including socio-economic indicators, drug co-use patterns, sex risks/work, BBV testing and status, and service utilization. Results emphasize the need for targeted special interventions and services for males and female crack users in Brazil.