Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinson's disease (PD), and a pilot clinical study using ¹⁸F‐dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2‐year, randomized, double‐blind, multinational study compared the rates of loss of dopamine‐terminal function in de novo patients with clinical and ¹⁸F‐dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen ¹⁸F‐dopa uptake (Ki) between baseline and 2‐year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region‐of‐interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (−13.4%; n = 68) compared with levodopa (−20.3%; n = 59; 95% confidence interval [CI], 0.65–13.06). Statistical parametric mapping localized lesser reductions in ¹⁸F‐dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, −14.1%; levodopa, −22.9%; 95% CI, 4.24–13.3), but the decrease was significantly lower with ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by ¹⁸F‐dopa PET. Ann Neurol 2003