The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) operated successfully during a 250 hr flight over Antarctica in 2006 December (BLAST06). As part of the calibration and pointing procedures, the red hypergiant star VY CMa was observed and used as the primary calibrator. Details of the overall BLAST06 calibration procedure are discussed. The 1σ uncertainty on the absolute calibration is accurate to 9.5%, 8.7%, and 9.2% at the 250, 350, and 500 μm bands, respectively. The errors are highly correlated between bands resulting in much lower errors for the derived shape of the 250–500 μm continuum. The overall pointing error is <5′′ rms for the 36′′, 42′′, and 60′′ beams. The performance of optics and pointing systems is discussed.