Apoptosis is a process of cell death, in which a cell commits suicide. Apoptosis is essential for the maintenance of homeostasis and apoptotic dysregulation has been implicated numerous human diseases. Apoptotic events are mediated through a unique family of aspartyl proteases, caspases. Our study tested the effectiveness of nontoxic, O-phenoxy-conjugates caspase inhibitors to prevent cell death. Human leukemia cells were treated with Boc-D(OMe)-OPh, Cbz-D(OMe)-OPh, Q-D(OMe)-OPh, Boc-VD(OMe)-OPh, Cbz-VD(OMe)-OPh, Q-VD(OMe)-OPh, and Q-VE(OMe)-OPh. The cells were induced to undergo apoptosis and the inhibitory effectiveness of the compounds was evaluated. Our results indicate the drugs that contained the dipeptide VD were more effective at inhibiting cell death than those that contained aspartic acid (D) alone. Q-VE(OMe)-OPh had no apoptotic inhibitory activity and was identified as the first true O-phenoxy conjugate, negative control. Our data suggest that N-terminal protecting groups and amino acid composition significantly alter the effectiveness of peptide-based cell death inhibitors.