The purpose of this study was to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects (N = 404) were randomly assigned to initial treatment with rasagiline (early-start group) or placebo for 6 months followed by rasagiline (delayed-start group) in the TEMPO study. Subjects who chose to participate in an open-label extension (N = 306) continued to receive rasagiline as well as other PD medications as needed. Average (±SD) duration in the study was 3.6 ± 2.1 years; 177 subjects received rasagiline for ≥5.0 years. Over the entire 6.5-year follow-up period, the adjusted mean difference in change from baseline in total UPDRS scores was 2.5 units (SE 1.1; P 5 0.021) or 16% (SE 5.7; P 5 0.006) in favor of the early-start versus delayed-start rasagiline group. Although the interaction between treatment and time was signi.cant, values for the early-start group were better than the delayed-start group across all time points. Significantly less worsening (percent change) in total UPDRS scores was observed in the early-start group at the time points 0.5, 1.5, 2.0, 3.0, 4.5, 5.0, and 5.5 years (P < 0.05). Compared to delayed start, early initiation of rasagiline provided long-term clinical benefit, even in the face of treatment with other dopaminergic agents. This might re.ect enduring benefits due to neuroprotection or effects on compensatory mechanisms in early PD. © 2008 Movement Disorder Society.