To conduct an indirect treatment comparison (ITC) of 2 approved routes of apomorphine administration for the on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD): apomorphine sublingual film (APL-130277; APL) and apomorphine subcutaneous injection (apo-SC). A systematic literature review was conducted and updated until 20May2020 to identify relevant randomized controlled trials. Eight studies were identified, which varied in design (eg, duration, placebo arm, assessment methods, etc). Outcomes included: (1) change from baseline in Part III score of Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) for APL or UPDRS for apo-SC, (2) mean reduction in “OFF” time (determined by patient-reported “OFF”/FULL “ON” status at discrete timepoints between 0–90 minutes for APL or by mean number of treated “OFF” episodes/day multiplied by mean reduction in “OFF” time/episode due to therapy as reported in patient diaries for apo-SC), and (3) the proportion of patients who turned FULLY “ON” (for APL) or “ON” (for apo-SC) based on patient diaries. ITC feasibility was assessed based on data availability and heterogeneity across studies. Apo-SC had a more favorable mean change in UPDRS Part III score at 20 minutes postdose vs APL in MDS-UPDRS Part III score at 30 minutes postdose (mean difference [95% credible interval], –12.4 [–17.2, –7.6]), APL and apo-SC had similar response estimates at 60 minutes postdose (–0.5 [–8.0, 7.0]), and APL had a more favorable response estimate vs apo-SC at 90 minutes postdose (–8.2 [–15.0, –1.4]). APL and apo-SC had a similar estimated mean reduction in “OFF” time (mean difference [95% credible interval], 4.38 minutes [–7.5, 16.2]). Data limitations prevented ITCs for the proportion of patients who turned FULLY “ON”/“ON.” ITCs suggest that APL may provide comparable efficacy to apo-SC, therefore other factors, such as route of administration, may influence specific treatment decisions.