IMPORTANCE Identification of the genetic risk factors that contribute to geographic atrophy (GA) could lead to advancements in interventional trials and/or therapeutic approaches for combating vision loss. OBJECTIVE To investigate whether single-nucleotide polymorphisms (SNPs) are associated with the presence and progression of established GA in age-related macular degeneration (AMD). DESIGN, SETTING, AND PARTICIPANTS Prospective, controlled, multicenter study of 154 patients with GA/AMD and 141 age-matched control participants at 8 Spanish hospitals. MAIN OUTCOMES AND MEASURES Samples of DNA were collected to analyze SNPs within AMD-related genes (CFH, CFB, C3, FHR1-3, and ARMS2). Fundus autofluorescence imaging was used to evaluate GA progression during a 2-year period in 73 patients with GA/AMD. Finally, logistic regression was used to analyze the associations of SNPs, age, body mass index, and cigarette smoking with the rate of progression and relative growth of GA. RESULTS This case-control analysis revealed a significant (P < .05) association between the presence of GA and SNPs within CFH, ARMS2, and FHR1-3. Moreover, logistic regression analysis identified significant associations of the rate of progression with genetic polymorphisms (CFH-402His [P = .04] and CFH-62Ile [P = .04]) and demographic factors (sex [P = .02] and age [P = .02]), whereas relative growth was associated with 1 polymorphism (CFB-32Gln [P = .04]). CONCLUSIONS AND RELEVANCE Taken together, our findings confirm that genetic risk factors related to the presence of GA are not identical to those associated with GA progression. In fact, we demonstrate that gene variants of CFH and CFB, as well as demographic risk factors, confer significant risk for GA progression (both rate of progression and relative growth) within a Spanish population.