Purpose To quantify the temporal properties of the acquired vitelliform lesion (AVL) life cycle, define the clinical characteristics of choroidal neovascularization (NV) in this setting, and determine the predictors of long-term visual outcomes. Design Retrospective cohort study. Methods Clinical and imaging data from 199 eyes of 124 consecutive patients with AVLs associated with age-related macular degeneration (AMD) and adult-onset foveomacular vitelliform dystrophy (AOFVD) were analyzed. Volumetric calculations of vitelliform material were determined using spectral-domain optical coherence tomography and the temporal properties of the AVL life cycle were quantified. The clinical characteristics of NV were assessed, as were the predictors of final best-corrected visual acuity (BCVA) and change in BCVA. Results Mean age was 79.2 ± 12.1 years. AVLs grew and collapsed at approximately the same rate (P = .275). Fifteen eyes (7.5%) developed NV, of which all were type 1. In 13 of these eyes, NV occurred during the collapse phase of the AVL life cycle, after the peak AVL volume was reached. The risk of NV (P = .006) and the decline in BCVA (P = .001) were both significantly greater among eyes with AMD. Foveal atrophy was the characteristic most significantly associated with final BCVA and change in BCVA from baseline (both P < .0005). The development of NV was not predictive of long-term visual outcomes (all P = .216). Conclusions Complications associated with AVLs typically occur during the collapse phase of the AVL life cycle. Visual outcomes and risk of NV are related to the underlying disease associated with AVLs.