Aims: To examine variability and effectiveness of interventions provided to comparator (control) groups in smoking cessation trials. Methods: Systematic review with meta-analysis of randomized controlled trials (RCTs) of behavioral interventions for smoking cessation, with or without stop-smoking medication. We searched the Cochrane Tobacco Addiction Group Specialized Register for RCTs with objective outcomes measured at ≥ 6 months. Study authors were contacted to obtain comprehensive descriptions of their comparator interventions. Meta-regression analyses examined the relationships of smoking cessation rates with stop-smoking medication and behavior change techniques. Results: One hundred and four of 142 eligible comparator groups (n = 23 706) had complete data and were included in analyses. There was considerable variability in the number of behavior change techniques delivered [mean = 15.97, standard deviation (SD) = 13.54, range = 0–45] and the provision of smoking cessation medication (43% of groups received medication) throughout and within categories of comparator groups (e.g. usual care, brief advice). Higher smoking cessation rates were predicted by provision of medication [B = 0.334, 95% confidence interval (CI) = 0.030–0.638, P = 0.031] and number of behavior change techniques included (B = 0.020, 95% CI = 0.008–0.032, P < 0.001). Modelled cessation rates in comparator groups that received the most intensive support were 15 percentage points higher than those that received the least (23 versus 8%). Conclusions: Interventions delivered to comparator groups in smoking cessation randomized controlled trials vary considerably in content, and cessation rates are strongly predicted by stop-smoking medication and number of behavior change techniques delivered.