The co-use of tobacco and cannabis is a common practice worldwide and carries with it substantial public health burden. Few interventions exist that target both substances and little is known about quit interest, treatment preferences, and drug substitution during past cessation attempts, which is critical to guide the development of treatment strategies. The goal of this study was to provide descriptive information regarding quit interest, treatment preferences, and perceived drug substitution among adult (age 18 +) cannabis-tobacco co-users. Participants (N = 282) from two independent survey samples (recruited from Amazon Mechanical Turk) from across the United States were combined. Among all participants, 57% were female, 79% were White, and average age was 33.31 (SD = 9.54) years old. Approximately 80% had tried to quit smoking cigarettes at least once, while 40% had tried to quit using cannabis at least once. Of those who tried to quit, 50% self-reported a perceived increase in their cannabis use during tobacco cessation and 62% self-reported a perceived increase in their tobacco use during cannabis cessation. Average quit interest (10-point scale) for cannabis was 2.39 (SD = 2.35) and for tobacco was 7.07 (SD = 2.90). Results of this study suggest that tobacco use should be addressed among cannabis-tobacco co-users, but interventions should consider lack of interest in cannabis cessation. Reduction-based strategies for cannabis use appear to be more acceptable to this nontreatment-seeking, co-using population. Drug substitution during quit attempts for one substance should be further explored as an important treatment consideration. (PsycINFO Database Record (c) 2019 APA, all rights reserved).