Mild and efficient methods for site-specific methylation of peptide backbone amides are important tools for chemists seeking to modulate the pharmacokinetic properties of peptide drugs. The Mitsunobu reaction was used to selectively methylate N-trifluoroacetamide (Tfa) protected peptides on-resin. The Tfa group was removed quickly and completely by reduction with excess NaBH4, and it was shown to be orthogonal to many of the protecting groups used in solid-phase peptide synthesis.