To identify when smoking cessation treatments affect craving, negative affect and anhedonia, and how these symptoms relate to abstinence, to help evaluate the effects of particular intervention components in multi-component treatments and accelerate treatment refinement. Secondary analysis of data from a two-arm randomized controlled trial. Seven primary care clinics in Wisconsin, United States. Adult primary care patients who smoked daily (n=574). Intervention was abstinence-optimized treatment (A-OT, n=276) comprising 3weeks of nicotine mini-lozenges pre-target quit day (TQD), 26weeks of combination nicotine patch and mini-lozenges post-TQD and extensive psychosocial support. The comparator was recommended usual care (RUC, n=298), comprising brief counseling and 8weeks of nicotine patch post-TQD. Time-varying effect models examined dynamic effects of A-OT (versus RUC) on the primary outcomes of nightly cigarette craving, negative affect and anhedonia from 1week pre- to 2weeks post-TQD. Exploratory models examined within-person relations between nicotine medication use and same-day symptom ratings. Secondary logistic regression analyses examined associations between post-TQD craving, negative affect and anhedonia and 1-month post-TQD abstinence. A-OT significantly suppressed pre- and post-TQD craving (β=-0.27 to -0.46 across days) and post-TQD anhedonia (β=-0.24 to -0.38 across days), relative to RUC. Within individuals, using patches was associated with lower negative affect in RUC (β=-0.42 to -0.52), but not in A-OT. Using more mini-lozenges was associated with greater craving (β=0.04-0.07) and negative affect (β=0.03-0.05) early, and with lower anhedonia (β=-0.06 to -0.12) later. Greater post-TQD craving (OR=0.68) and anhedonia (OR=0.85) predicted lower odds of abstinence 1month post-TQD. Time-varying effect models showed that a multi-component treatment intervention for smoking cessation suppressed significant withdrawal symptoms more effectively than recommended usual care among daily adult smokers motivated to quit. The intervention reduced craving pre- and post-target quit day (TQD) and anhedonia post-TQD.