Abstract The majority of women who quit smoking during pregnancy relapse postpartum and many experience increased depressive symptoms and concerns about body shape and weight. Given the relationship of weight concerns and negative mood to smoking relapse, interventions designed to address the postpartum experience are indicated. However, there are several challenges to research with postpartum women. We describe the rationale of a randomized controlled trial of postpartum smoking relapse prevention intervention and discuss methods to address the specific challenges to recruiting, retaining and conducting health behavior interventions among postpartum former smokers. Pregnant women who had quit smoking for at least one month prior to the 34week of pregnancy and who were motivated to stay quit postpartum were recruited. Women were randomized either to a postpartum specific intervention designed to address concerns about mood, stress and weight using cognitive-behavioral techniques or to a support-only condition designed to control for time and attention. Intervention continues through six months postpartum and women complete follow-up assessments at 12-, 24- and 52-weeks after delivery. Women (n=300) who had quit smoking as a result of pregnancy were recruited and are being followed. The intervention described in this report is designed to address stress, negative mood and concerns about weight that mediate smoking relapse postpartum to sustain abstinence and improve maternal and infant health.