Substance use is strongly associated with HIV risk among gay men. Many gay couples establish sexual agreements. However, little is known about gay couples' use of substances with sex, and whether substance use is associated with couples' agreements. The present study assessed whether gay couples' use of substances with sex was associated with their establishment of, type of, and adherence to, a sexual agreement. Dyadic data from 275 HIV-negative US gay couples were collected online in a nation-wide, cross-sectional study, and analyzed at the couple-level. Findings revealed that couples with an established agreement, and a recently broken agreement, were more likely to have used amyl nitrates and marijuana with sex within their relationship. This same trend was also noted, but for alcohol use with sex outside of couples' relationships. Further research is urgently needed to examine the fluidity of HIV-negative gay male couples' sexual agreements and substance use with sex.