OBJECTIVES: Parkinson’s disease (PD) is a progressive disease associated with substantial economic and societal burden.  Immediate-release (IR) carbidopa-levodopa (CD-LD) is the gold standard in treatment for advanced PD patients.  However, effectiveness of IR CD-LD diminishes with long-term treatment and is associated with increased “off” time (re-emergence of PD symptoms) and the advent of motor complications.  CD-LD plus entacapone (CL+E) has produced some clinical improvement over IR CD-LD alone. IPX066 is an extended-release oral formulation of CD-LD designed to address some of the limitations of IR CD-LD by rapidly attaining and maintaining therapeutic LD concentrations for a prolonged duration.  The aim of the study was to evaluate the comparative cost-effectiveness of IPX066 against CL+E. METHODS: A Markov model was developed comparing IPX066 with branded and generic CL+E in the US market.  Health states included ≤ 25% “off” time, > 25% “off” time, and dead.  The model simulated a hypothetical patient’s progression over a 5-year period through these health states, with a 6-month Markov cycle length. Outcomes evaluated were total direct costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER).  Dosing and efficacy data from a Phase 3 study comparing IPX066 and CL+E, average wholesale acquisition drug costs (RedBook), and published literature were utilized for this evaluation.  Non-2014 costs were inflated to reflect the 2014 value using the medical component of the Consumer Price Index.  The discount rate employed was 3%. RESULTS: IPX066 was dominant over both branded and generic CL+E therapies, with ICERs of (-$166,044) and (-$75,920), respectively.  On average, patients who received IPX066 experienced a 5.1% increase in QALYs (2.90) compared with patients who did not receive IPX066 (2.76).  IPX066 dominated the other two therapies throughout multiple sensitivity analyses, driven largely by improved effectiveness of IPX066. CONCLUSIONS: IPX066 is likely to be a cost-effective therapy in patients with advanced PD.