To report the five-year outcomes from the ILLUMENATE Pivotal Randomized Controlled Trial (RCT) of the lower dose (2 µg/mm2) Stellarex drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic peripheral arterial disease (PAD). Long-term safety and effectiveness data for DCBs remains limited. ILLUMENATE Pivotal was a prospective, randomized, multi-center, single-blinded study. Patients (Rutherford 2-4) were randomized 2:1 to Stellarex DCB or PTA. Follow-up was through 60 months. Three hundred patients were enrolled. The mean age was 68.8 ± 10.2 years. At 60-months, freedom from a primary safety event was in 69.2% in the Stellarex DCB arm and 68.2% in the PTA arm (log rank, P=0.623). The cumulative rate of major adverse events was 41.0% compared with 44.6% (P=0.597), respectively. Freedom from clinically driven-target lesion revascularization (CD-TLR) was 70.3% in the Stellarex DCB arm compared with 68.2% in the PTA arm (P=0.505). Time to first CD-TLR was 768.3 ± 478.9 days compared with 613.5 ± 453.4 days, respectively (P=0.161). Kaplan-Meier estimates of freedom from all-cause mortality were 80.1% in the Stellarex DCB arm and 80.2% in the PTA arm (log rank, P=0.980). The five-year results of the ILLUMENATE Pivotal RCT add to the consistent safety data from the broader ILLUMENATE clinical program. These are the first data to report the five-year safety and efficacy of a lower dose (2 µg/mm2) DCB for the treatment of symptomatic PAD. ILLUMENATE Pivotal was a multi-center, single-blinded RCT which assessed the lower dose (2 µg/mm2) Stellarex drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic peripheral arterial disease. At five years, the Stellarex DCB showed similar freedom from clinically driven-target lesion revascularization (70.3% versus 68.2%; P=0.505) and no difference in all-cause mortality (80.1% versus 80.2%; log rank, P=0.980) compared with PTA. These results reinforce the previously established safety of the Stellarex DCB from the broader ILLUMENATE clinical program. Importantly, this the first report of five-year safety and effectiveness outcomes for a lower dose (2 µg/mm2) DCB.