Although substance use is linked to HIV seroconversion, little is known about male couples substance use with sex. The present study sought to: describe whether neither, one, or both partners in the couple used a particular substance with sex within or outside their relationship; assess, by substance type used with sex, whether relationship factors differed between these groups of couples. Dyadic data from 83 behaviorally non-monogamous HIV-negative male couples were used with multinomial regression models. Those who used with sex within the relationship varied by substance type; outside the relationship, most only had one partner who used with sex. Couples with one or both partners who used substances with sex within or outside the relationship were more likely to have higher commitment to their relationship yet less likely to trust their main partner; mixed results were found regarding communication. Further research is warranted toward the need for preventive intervention development.