Purpose: To establish the predictive value of defined retinal morphologic parameters on visual outcomes and re-treatment needs in patients with neovascular age-related macular degeneration (nAMD) receiving ranibizumab treatment. Design: Post hoc analysis of a prospective, 12-month, multicenter, phase IIIb trial. Participants: Three hundred fifty-three treatment-naive patients with nAMD. Methods: Available data from 319 treatment-naive patients receiving ranibizumab 0.3 mg monthly (frequent regimen; n = 102) or ranibizumab 0.3 or 0.5 mg quarterly (pooled 0.3/0.5 mg = infrequent regimen; n = 217) were analyzed to assess the correlations between baseline retinal morphologic parameters and best-corrected visual acuity (BCVA) change (structure-function correlations). The BCVA was measured at monthly visits. Optical coherence tomography scans were acquired monthly for quantitative measures of the central retinal thickness and qualitative assessment of retinal morphologic features. Assessed morphologic parameters included intraretinal cystoid fluid (IRC), subretinal fluid (SRF), pigment epithelial detachment, and vitreomacular interface configuration classification comprising vitreomacular adhesion and posterior vitreous detachment (PVD). An analysis of covariance was conducted to evaluate the impact of retinal morphologic features on BCVA change at month 12. Main Outcome Measures: Change in BCVA from baseline to month 12 compared between frequent and infrequent treatment arms. Results: Relevant predictive factors for BCVA change at month 12 were baseline SRF (P = 0.05), PVD (P = 0.03), IRC (P = 0.05), treatment frequency (P < 0.01), and BCVA (P < 0.01). The presence of both SRF and PVD at baseline was associated with similar BCVA gains regardless of treatment frequency (mean difference in BCVA gains at month 12 of +2.6 letters in favor of infrequent treatment). Subretinal fluid was present in 71% of patients, and PVD was present in 64% of patients. Conclusions: In patients with both SRF and PVD at baseline, similar BCVA outcomes were observed regardless of treatment frequency. These patients may require less frequent treatments compared with patients without SRF, without PVD, or without either who may require more frequent injections for maintenance of vision. This finding may have implications in clinical practice by helping to tailor an individualized retreatment interval in nAMD patients. (C) 2016 by the American Academy of Ophthalmology.