To compare the knowledge, beliefs, and practices regarding HPV vaccination among mothers of vaccine-eligible girls in Mexico and the USA.Similar samples of Mexican mothers with vaccine-eligible daughters were surveyed at two clinics in Cuernavaca, Morelos, from July to October 2012 (n = 200) and at two clinics in Oxnard, California, from August to November 2013 (n = 200).Although mothers in the USA had less knowledge and more negative attitudes toward the vaccine than their counterparts in Mexico, vaccine uptake rates were higher in the USA (49% vs. 40%). US mothers were more likely to have discussed and been offered the HPV vaccine by a clinician than mothers in Mexico. In multivariate analyses, having been offered the HPV vaccine was the most important predictor of vaccine uptake.Our results suggest that healthcare access or other system, clinic, or provider factors are the main drivers of vaccine receipt in this binational sample of Mexican mothers. Interventions and programs that encourage clinicians to offer the HPV vaccine should be developed to increase vaccine uptake in both countries.