Although smokers with co-occurring pain report expectations for experiencing greater nicotine withdrawal and difficulty quitting, limited work has examined the role of pain in cessation-related outcomes. The goal of this study was to examine clinically relevant pain characteristics (pain persistence, pain intensity, pain-related disability) as predictors of withdrawal and smoking lapse/relapse outcomes using a laboratory paradigm of cessation. Participants ( = 120 daily cigarette smokers; 48% male; = 36.17, SD = 12.16; = 20.51, SD = 6.99) were randomized to either nondeprived or 12-hr nicotine deprivation conditions prior to an experimental study visit. Upon arrival to the laboratory, participants completed measures of pain characteristics and nicotine withdrawal symptoms. Primary outcomes included nicotine withdrawal scores and analogues of smoking lapse (latency to initiating smoking) and relapse (number of cigarettes smoked). We hypothesized that smokers with greater pain persistence, pain intensity, and pain-related disability would endorse more severe nicotine withdrawal and greater lapse/relapse behavior, and that these positive associations would be stronger among those who were nicotine deprived. Results indicated that, above and beyond the effect of nicotine deprivation, persistent pain predicted more severe nicotine withdrawal, and that greater pain-related disability predicted quicker latency to lapse during the laboratory paradigm. Contrary to expectation, nicotine deprivation did not moderate effects of pain characteristics on withdrawal or lapse/relapse outcomes. Clinical implications include that different pain processes may influence different cessation outcomes, and that smokers in pain may benefit from the provision of pharmacological aids to better control withdrawal symptoms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).