Several studies have addressed the effect of the Sp1 polymorphism of the collagen Iα 1 (COLIA1) gene on the prevalence of fractures. The results are not in full agreement on whether this polymorphism is associated with fracture risk. To clarify this uncertainty, we performed a meta-analysis including 13 eligible studies with 3641 subjects. The COLIA1 Sp1 polymorphism showed a dose-response relationship with the prevalence of fractures. The risk was 1.25-fold (95% CI, 1.09–1.45) in Ss heterozygotes versus SS homozygotes, 1.68-fold (95% CI, 1.35–2.10) in ss homozygotes versus SS> homozygotes, and 1.35 (95% CI, 1.04–1.75) for ss homozygotes versus Ss heterozygotes by random effects calculations. There was modest heterogeneity for these three effect estimates (p value for heterogeneity, 0.17, 0.16, and 0.08, respectively). The Sp1 polymorphism effects possibly were larger when the analysis was limited to studies considering only vertebral fractures (pooled risk ratios [RR], 1.30, 2.07, and 1.46, respectively). Conversely, the Sp1 polymorphism effects tended to be smaller in studies with mean patient age ≥65 years than in studies with younger patients on average, but the differences were not formally significant. We estimated the total average attributable fraction (AF) of fractures due to the s allele in European/U.S. populations as 9.4%. The meta-analysis suggests an important role for the Sp1 polymorphism in the regulation of fracture risk; however, potential heterogeneity across ethnic groups, age groups, and skeletal sites may be important to clarify in future studies. Very large studies or meta-analyses are required to document subtle genetic differences in fracture risk.