There is a well-recognised relationship between body weight, plantar pressures and foot pain, but the temporal association between these factors is unknown. The aim of this study was to investigate the relationships between increasing weight, plantar pressures and foot pain over a two-year period.Fifty-one participants (33 women and 18 men) completed the two-year longitudinal cohort study. The sample had a mean (standard deviation (SD)) age of 52.6 (8.5) years. At baseline and follow-up, participants completed the Manchester Foot Pain and Disability Index questionnaire, and underwent anthropometric measures, including body weight, body mass index, and dynamic plantar pressures. Within-group analyses examined differences in body weight, foot pain and plantar pressures between baseline and follow up, and multivariate regression analysis examined associations between change in body weight, foot pain and plantar pressure. Path analysis assessed the total impact of both the direct and indirect effects of change in body weight on plantar pressure and pain variables.Mean (SD) body weight increased from 80.3 (19.3), to 82.3 (20.6) kg, p = 0.016 from baseline to follow up. The change in body weight ranged from -16.1 to 12.7 kg. The heel was the only site to exhibit increased peak plantar pressures between baseline and follow up. After adjustment for age, gender and change in contact time (where appropriate), there were significant associations between: (i) change in body weight and changes in midfoot plantar pressure (B = 4.648, p = 0.038) and functional limitation (B = 0.409, p = 0.010), (ii) plantar pressure change in the heel and both functional limitation (B = 4.054, p = 0.013) and pain intensity (B = 1.831, p = 0.006), (iii) plantar pressure change in the midfoot and both functional limitation (B = 4.505, p = 0.018) and pain intensity (B = 1.913, p = 0.015). Path analysis indicated that the effect of increasing body weight on foot-related functional limitation and foot pain intensity may be mediated by increased plantar pressure in the midfoot.These findings suggest that as body weight and plantar pressure increase, foot pain increases, and that the midfoot may be the most vulnerable site for pressure-related pain.