Background Existing systematic reviews have concluded that psycho-educational interventions for smoking relapse prevention were ineffective. Our objective was to conduct an exploratory meta-analysis, guided by mechanisms of these complex interventions for preventing smoking relapse. Methods Relevant trials were identified from a Cochrane review and by an updated search of MEDLINE and PsycINFO (up to August 2009). We examined theories or mechanisms underlying relapse prevention interventions, and process variables reported in trials. Odds ratios (ORs) for the rate of smoking abstinence at the longest follow-up were pooled in meta-analysis. Results Forty-nine trials were included, and interventions were at least partly based on the cognitive-behavioural approach to coping skills training in 41 trials. Only a few trials reported data on process variables. Coping skills training for smoking relapse prevention was effective for community quitters (OR 1.27, 95% CI: 1.08–1.49), and particularly for those who stopped smoking for at least 1 week at baseline (OR 1.52, 95% CI: 1.20–1.93). These findings were interpretable with mechanisms of coping skills training for relapse prevention. Conclusions On the basis of post hoc subgroup analyses, coping skills training for smoking relapse prevention is effective for motivated community quitters. This finding has important public health implications and needs to be confirmed by further trials.