Importance In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV). Objective To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial. Design, Setting, and Participants This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022. Interventions Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits. Main Outcomes and Measures Least-squares (LS) mean change in BCVA from baseline at week 48. Results A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, −4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; −0.7; 95% CI, −4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48. Conclusions and Relevance Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV. Trial Registration ClinicalTrials.gov Identifier: NCT04423718