Fragment linking is the process of linking two fragments that bind at distinct sites on a protein and can entail multiplicative increases in affinity; taking a micromolar binding fragment to a nanomolar lead. Fragment linking was a seminal concept in FBDD in Stephen Fesik’s landmark paper describing SAR by NMR (1). However, optimization through fragment linking is now unpopular due to often lengthy syntheses and low success rates, leading to the perception that linking is to be avoided as a slow and largely inefficient process. A recent method to address these issues is off rate screening (ORS) by Surface Plasmon Resonance (SPR) (2). The recent development of ORS is both time and resource efficient. However, it remained to be validated for fragment linking. Here, we present a highly efficient strategy for hit optimisation via fragment linking using ORS by SPR. Diverse linkers with amenable handles were first identified and fragment monomers with complementary reactive groups were designed accordingly. Given the key failing point of fragment linking is lengthy synthesis, we synthesised 13 dimers on a small scale with minimal purification. We then determine the tightest binders via ORS. The concentration independent off-rates of protein-ligand interactions enables testing of crude reaction mixtures, as the tightest binder will demonstrate markedly slower dissociation kinetics compared to the starting materials. Using this technique we identified mixtures with that gave good response heights and slow dissociation kinetics by SPR. We then re-synthesised these on batch scale and tested the pure compounds, discovering 4 compounds with KD < 500 nM. These included a promising lead candidate with a 13 nM affinity; amounting to an approximately 10,000 fold increase in affinity over the starting monomers in a period of just a few months; demonstrating how efficiently linking monomers can generate a high affinity compound.