Although an estimated 25% of premenopausal smokers report using oral contraceptives (OC), little is known about how OC use may influence smoking cessation. The purpose of this study was to examine the difference in smoking-related symptomatology during acute smoking abstinence between women on a standardized combination OC (Tri-Sprintec™) compared to women not on OCs (no-OC).Participants were women aged 18–40 who smoked ≥5 cigarettes/day and reported regular menstrual cycles. Using a controlled cross-over design, participants completed two six-day testing weeks: Low Progesterone Week (LPW; Follicular (F) phase in no-OC or 1st week of pills in OC) and High Progesterone Week (HPW; Luteal (L) phase in no-OC or 3rd week of pills in OC). Each testing week included daily assessment of symptomatology and biochemical confirmation of smoking status.During smoking abstinence, the OC group (n=14) reported significantly lower levels of positive affect (21.56±7.12 vs. 24.57±6.46; β=3.63, p=0.0323) than the no-OC group (n=28). Further significant interactions between group and testing week were observed as follows: Smoking satisfaction was higher during LPW in the OC group (LPW: 4.29±1.30 vs. HPW: 4.10±1.37) but higher during HPW in the no-OC group (LPW: 3.91±1.30 vs. HPW: 4.23±1.30; β=−0.5499, p<0.0001). Similar interactions were noted in negative affect and psychological reward of smoking.These results suggest that women on OCs may have different patterns of smoking-related symptomatology during short-term smoking abstinence as compared to women not on OCs. Additional work is needed to examine how this may affect smoking cessation efforts.