BACKGROUND:We aimed to compare indicators of Parkinson disease (PD) progression between patients first prescribed either selegiline or rasagiline as their antiparkinsonian drugs (APDs) on the basis of real-life data. METHODS:Pharmacy data on members of a large Israeli health maintenance organization, treated as patients with PD during 2001-2012 and prescribed selegiline or rasagiline as their first APD, were analyzed. The first APD was selegiline for 349 patients (2001-2006) and rasagiline for 485 patients (2007-2012). Time from monoamine oxidase type B inhibitor prescription until initiating treatment with dopamine agonists (DAs) or levodopa was compared between the groups using Cox regression adjusted to sex and age at initiation of APD. RESULTS:The selegiline group was significantly older at first monoamine oxidase type B inhibitor purchase. In a similar follow-up time (3.0 [1.7] year for selegiline group, 3.1 y [1.4] for rasagiline group), the time to initiation of levodopa treatment did not differ between the 2 groups (adjusted hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.86-1.31). The time to initiation of DA treatment was longer in the selegiline group (adjusted HR, 1.93; 95% CI, 1.49-2.53). For those who were treated with DA before levodopa (n = 276), the time to initiation of levodopa treatment was longer in the rasagiline group (adjusted HR, 0.77; 95% CI, 0.56-1.07). CONCLUSIONS:The similarity in time to levodopa in both groups suggests no differences between selegiline and rasagiline in their effect on the natural history of PD. A possible interaction effect between rasagiline and DA might exist. A better symptomatic profile of selegiline more than that of rasagiline in the earlier stages of PD may explain the difference between the 2 groups in time to DA initiation.