OBJECTIVE: To describe predominantly persistent subretinal fluid (SRF) in eyes receiving ranibizumab or bevacizumab for neovascular age-related macular degeneration and to compare visual acuity (VA) to eyes with nonpersistent SRF. DESIGN: Cohort within randomized clinical trial. PARTICIPANTS: Comparison of Age-related Macular Degeneration Treatments Trials patients assigned to pro re nata treatment. METHODS: Graders evaluated monthly OCT scans for SRF. Predominantly persistent SRF through week 12 was defined as SRF at baseline and weeks 4, 8, and 12. Predominantly persistent SRF through 1 or 2 years was defined as SRF in 80% or more of visits by years 1 or 2, respectively. Linear regression models including baseline predictors of VA and predominantly persistent intraretinal fluid (IRF) were used to evaluate mean differences in vision outcomes. PRIMARY OUTCOME MEASURES: Predominantly persistent SRF through year 1, adjusted VA score and VA change, and foveal SRF thickness. RESULTS: Among 406 eyes with baseline SRF, SRF persisted in 108 eyes (26.6%) through week 12, in 94 eyes (23.2%) through year 1, and in 77 eyes (19.0%) through year 2. Adjusted VA means at year 1 were similar between eyes with predominantly persistent versus non persistent SRF by week 12 (68.1 vs. 70.2 letters; P = 0.18), year 1 (67.6 vs. 70.2 letters; P = 0.11), and year 2 (71.4 vs. 70.9 letters; P = 0.78). Adjusted changes in mean VA at year 1 were similar between eyes with predominantly persistent versus nonpersistent SRF by week 12 (6.3 vs. 7.6 letters; P = 0.38), year 1 (5.5 vs. 7.8 letters; P = 0.14), and year 2 (8.1 vs. 7.7 letters; P = 0.78). Among eyes with predominantly persistent SRF through year 1, foveal SRF was absent in 46 eyes (48.9%), thickness was 1 to 200 μm in 48 eyes (50.0%) and more than 200 μm in 1 eye (1.1%) at year 1. CONCLUSIONS: Eyes with predominantly persistent and nonpersistent SRF through week 12, year 1, or year 2 showed similar VA outcomes after adjustment for baseline covariates and persistent IRF. At the foveal center, predominantly persistent SRF was most commonly absent or present in small quantities.