Objective.To investigate whether high molecular weight adiponectin (hmwAPN) mediates the associations of total adiponectin (totAPN) with radiographic progression in rheumatoid arthritis (RA) and hand osteoarthritis (HOA).Methods.Associations between baseline hmwAPN or totAPN levels with radiographic progression were determined using multivariate linear regression or generalized estimated equations.Results.In patients with RA, totAPN associated positively, whereas in patients with HOA it associated negatively with radiographic progression. In contrast, hmwAPN did not associate significantly with radiographic progression in either cohort.Conclusion.Our data indicate that the differential effects associated between totAPN and radiographic progression in either RA or HOA are not mediated by hmwAPN.