Introduction: Carbidopa-levodopa extended-release capsules (ER CD-LD, IPX066) significantly improves motor symptoms and activities of daily living in early and advanced Parkinson’s disease (PD). ER CD-LD produces an initial peak in plasma levodopa concentrations at about one hour, which are maintained for about 4–5 hours before declining. Methods: The safety and efficacy of ER CD-LD vs. immediate-release (IR) CD-LD was examined in a randomized, double-blind, active-controlled, Phase 3 study. Efficacy measures (PD diary and Unified PD Rating Scale [UPDRS] Parts II [activities of daily living] + III [motor score]) were analyzed to evaluate the effect of concomitant use or non-use of dopamine agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, or amantadine on the response to ER CD-LD. Results: In the overall study (N=393), ER CD-LD improved “off” time (P<.0001), “on” time without troublesome dyskinesia (P=.0002), and UPDRS Parts II+III scores (P<.0001) vs. IR CD-LD. Numerical improvements from baseline in PD diary measures and UPDRS Parts II+III were seen with ER CD-LD vs. IR CD-LD in each subgroup. Improvements in “off” time and “on” time without troublesome dyskinesia were significant (P<.05) for ER CD-LD vs. IR in each subgroup, except for the group using concomitant amantadine (P>.50). ER CD-LD did not significantly worsen “on” time with troublesome dyskinesia vs. IR in any subgroup (P>.11). The most frequent adverse events were similarly reported across subgroups. Conclusions: The concomitant use or non-use of adjunctive PD medications did not affect the efficacy or degree of troublesome dyskinesias when ER CD-LD was compared to IR CD-LD.