To compare the repeatability and agreement of corneal thickness measurements using central and peripheral ultrasound and Orbscan pachymetry to detect contact lens (CL)-induced corneal swelling after extended wear (EW). Corneal thickness was measured in five corneal locations (central, superior, inferior, nasal, and temporal) with ultrasound and Orbscan pachymetry 1 week before CL wear commenced and after 1 week of EW. High oxygen permeability (lotrafilcon A) and low oxygen permeability (etafilcon A) CL were randomly fitted for EW in the right and left eyes of 20 subjects with normal ocular health to induce different amount of corneal swelling. Poor repeatability and poor agreement in peripheral ultrasound and Orbscan pachymetry was found between corneas with and without corneal swelling. Ultrasound coefficients of repeatability (central, superior, inferior, nasal, and temporal) in corneas without (0.95, 2.1, 3.2, 3.9, and 3.8%) and with (0.91, 1.89, 2.45, 2.66, and 2.26%) corneal swelling were higher than Orbscan coefficients of repeatability without (0.74, 1.67, 1.29, 1.11, and 1.11%) and with (0.74, 1.47, 1.28, 1.78, and 1.23%) corneal swelling. Lotrafilcon A induced significantly less corneal swelling in all five corneal locations compared with etafilcon A. Peripheral corneal swelling differences between lens types were significant only with Orbscan measurements (p < 0.05, Paired t-test and re-analysis of variance). The assessment of corneal thickness shows higher repeatability using Orbscan pachymetry than using ultrasound to measure corneas with and without corneal swelling and could be useful to study central and peripheral corneal swelling variations in CL EW.