MRI-based cartilage morphometry can monitor cartilage loss in osteoarthritis. Intravenous Gd-DTPA injection is needed for compositional (proteoglycan) cartilage imaging with delayed gadolinium enhanced MRI (dGEMRIC). However, longitudinal changes of cartilage morphology have not been compared in the presence and absence of Gd-DTPA. Baseline and 2-year follow-up images were acquired in 41 female participants with definite medial radiographic osteoarthritis, both before and 2 h after Gd-DTPA injection, and cartilage thickness was measured. In the absence of Gd-DTPA, a 2.6% reduction in cartilage thickness was observed between baseline and follow-up in the central subregion of the medial femorotibial compartment (standardized response mean [SRM]= -0.33; P<0.05), but only a 0.7% reduction (SRM= -0.10; P=0.51) in the presence of Gd-DTPA. The findings suggest that morphometric cartilage measurement in the presence of Gd-DTPA needs to undergo further validation, before one can recommend longitudinal dGEMRIC and morphological cartilage imaging to be performed in a single session.