Here, we present the design, synthesis, and mechanistic characterization of trivalent PROTACs as a strategy to enhance targeted protein degradation. We elected the Bromo and Extra Terminal (BET) domain family member proteins BRD2, BRD3 and BRD4 as ideal model systems for this study because of their therapeutic relevance in many diseases including cancer . Several bivalent BET inhibitors and PROTACs, including the afore-mentioned MZ1, have been developed from parent monovalent inhibitors . Altogether, these compounds provided suitable benchmark reference for our study, where we set out to synergize the effects of a bivalent target ligand with E3 ligase recruitment to produce a trivalent PROTAC with enhanced target degradation. Our trivalent PROTACs were further characterized in a series of biochemical, biophysical and cellular assays to understand potency, kinetics, and specificity of degradation as compared to bivalent molecules, as well as for functional outcomes and underlying mechanism of action.