PURPOSE To examine if the variability in hypoxic corneal swelling in non-contact lens wearing and contact lens wearing groups can be explained by the variability in corneal metabolic activity or endothelial function. METHODS Corneal thickness was measured by Orbscan before and after 2 hr of closed-eye hydrogel lens wear. De-swelling rates (percentage recovery per hour) were determined by continued corneal thickness measurements until open-eye steady-state thickness was reached. Corneal oxygen consumption was estimated by measuring tear oxygen tension while wearing hydrogels of known oxygen transmissibility. The change in stromal pH because of hypoxia was measured by ratio fluorescence of stromal fluorescein. RESULTS Corneal swelling was inversely correlated with open- or closed-eye tear oxygen tension while wearing the test hydrogels. Corneal swelling was directly correlated with the change in stromal pH during hypoxic lens wear. Unexpectedly, corneal swelling was also inversely correlated with the percent recovery per hour. These parameters could not explain all the swelling variability. The contact lens wearing group showed significantly less swelling and change in stromal pH with the same lenses. However, percent recovery per hour and tear oxygen tension was the same. CONCLUSION Corneal swelling is associated with corneal metabolic activity and endothelial function; however, other factors must also be involved. Contact lens wearers do not adapt by modifying oxygen consumption but probably by using glucose more efficiently.