We examine the variability of the high-ionization Ly{alpha} {lambda}1216 broad emission line (BEL) in a sample of 61 high-luminosity, high-redshift quasars observed at two epochs by the Sloan Digital Sky Survey. These bright objects lie in the redshift interval z=[2.5, 4.3] and have luminosities 3.4x10^45^<~{lambda}*L_{lambda}_<~3.4x10^46^erg/s at 1450{AA}. Utilizing improved spectrophotometric flux calibrations relative to nearby compact stars observed simultaneously, we are able to measure the flux changes in Ly{alpha} and the nearby continuum at two epochs. We find 20 objects that exhibit Ly{alpha} BEL flux variability at a significance level greater than 5{sigma} on time-scales ranging from days to years in the quasar rest frame.