Background: There is a paucity of data on the relationship between backpack use and foot posture in children. The aim of this study was to assess the effects of a backpack on foot posture in children with neutral foot posture during three years of follow-up. Methods: A prospective longitudinal observational study was conducted in a sample of 627 children with neutral foot. For each participant included in the study, age, sex, weight, height, body mass index, type of schoolbag (backpack or non-backpack), foot shape, metatarsal formula and type of shoes were recorded. Foot posture was described by the mean of the foot posture index (FPI) and reassessed after three years in a follow-up study. Results: The average age of the children was 8.32 ± 1.32 years. A total of 458 used a backpack when going to school. Over the three-year follow-up period, 50 children who had neutral foot developed supinated foot (n = 18) or pronated foot (n = 32). Univariate and multivariate analysis showed that the children using a backpack were at a higher risk of developing pronated foot (adjusted Odds Ratio (aOR) = 2.05, 95% IC: 1.08–3.89, p = 0.028). Backpack use was not associated with the change from neutral foot to supinated foot. Conclusions: We found a positive association between using a backpack and the risk of developing pronated but not supinated foot. Clinical trials should be conducted to analyze the effect of backpack use on the foot among schoolchildren.