Purpose: To compare central and peripheral corneal swelling with high-Dk (lotrafilcon Lambda) and low-Dk (etafilcon A) contact lenses (CLs) during extended wear (EW). Methods: Corneal thickness was measured in 5 cforneal location (central, superior, inferior, nasal and temporal) with Orbscan II pachymetry 1 week before the wearing of CLs and after 1 week of EW. High-Dk (lotrafilcon A) and low-Dk (etafilcon A) soft CLs were randomly fitted for EW in the right and left eyes of 20 subjects with normal ocular health. Orbscan was also performed before CL removal after 3 and 7 days of EW. Results: Ltrafilcon A induced a lower percentage of corneal swelling in all 5 corneal locations than etafilcon A (P < 0.05, paired t test). Lotrafilcon A swelling percentages were as follows: central (1.67% +/- 2.22%) (2.04% +/- 3.25%), inferior (1.38% +/- 1.74%), nasal (1.50% +/- 2.00%), and temporal (1.27% +/- 1.47%) Etafilcon A swelling percentages were as follows: central (4.98% +/- 3.07%), superior (6.62% +/- 8.39%), inferior (5.24% +/- 5.54%), nasal (3.41% +/- 3.14%), and temporal (4.46% +/- 3.32%). Differences between the central and peripheral corneal swelling during EW of both types of lenses were not significant (P > 0.05. repeatedly measures analysis of variance). Conclusions: Central and peripheral corneal thickness increase more with etafilcon A than with lotrafilcon A during EW as measured by Orbscan pachymetry.