To investigate the relation between contrast sensitivity function and ocular higher-order wavefront aberrations in normal human eyes. Prospective observational case series. Three hundred seven eyes of 161 normal subjects, ranging in age from 15 to 60 years (30.9+/-8.0 [mean +/- standard deviation]). Ocular higher-order aberrations were measured for a 4-mm pupil using the Hartmann-Shack wavefront analyzer. The root-mean-square of the third- and fourth-order Zernike coefficients was used to represent comalike and spherical-like aberrations, respectively. We measured contrast sensitivity, low-contrast visual acuity (VA), and letter contrast sensitivity. From the contrast sensitivity data, the area under the log contrast sensitivity function (AULCSF) was calculated. Pupil diameter in a photopic condition was recorded using a digital camera. Multiple linear regression analysis revealed that comalike aberration (P = 0.002) was significantly associated with AULCSF, but spherical-like aberration (P = 0.200), age (P = 0.185), and photopic pupil diameter (P=0.252) were not. Comalike aberration showed a significant correlation with low-contrast VA (P<0.001), but spherical-like aberration (P = 0.293), age (P = 0.266), and pupil diameter (P = 0.756) did not. Comalike aberration was found to be significantly associated with letter contrast sensitivity (P<0.001), but spherical-like aberration (P=0.082), age (P = 0.370), and pupil diameter (P = 0.160) were not. In normal human eyes, comalike aberration of the eye significantly influences contrast sensitivity function.