Several systematic reviews of school-based smoking prevention trials have shown short-term decreases in smoking prevalence but have not examined long-term follow-up evaluation. The purpose of this study was to conduct a systematic review of rigorously evaluated interventions for school-based smoking prevention with long-term follow-up data. We searched online bibliographic databases and reference lists from review articles and selected studies. We included all school-based, randomized, controlled trials of smoking prevention with follow-up evaluation to age 18 or 12th grade and at least 1 year after intervention ended, and that had smoking prevalence as a primary outcome. The primary outcome was current smoking prevalence (defined as at least 1 cigarette in the past month). The abstracts or full-text articles of 177 relevant studies were examined, of which 8 met the selection criteria. The 8 articles included studies differing in intervention intensity, presence of booster sessions, follow-up periods, and attrition rates. Only one study showed decreased smoking prevalence in the intervention group. Few studies have evaluated the long-term impact of school-based smoking prevention programs rigorously. Among the 8 programs that have follow-up data to age 18 or 12th grade, we found little to no evidence of long-term effectiveness.