In Solid Phase Peptide Synthesis (SPPS), contamination with deletion sequences which often co-elute with the target peptide continues to be a major challenge as these impurities can significantly affect the target peptide's properties. Here, we report an efficient Fmoc-deprotection solution containing piperazine and DBU which can cause complete removal of the Fmoc group in less than a minute. This combination rivals piperidine in speediness as revealed by kinetic studies. We demonstrate the efficiency of the piperazine/DBU solution by synthesizing the polyAla stretch with a significant reduction of deletion products occurring due to partial Fmoc deprotection. We verify the utility of the deprotection solution by successfully synthesizing four aggregation prone difficult peptide sequences. We further demonstrate that this combination can also be used to synthesize aspartimide and epimerization prone sequences when supplemented with 1% formic acid and is compatible with 2-chlorotrityl chloride resin. We conclude that piperazine/DBU can be used as a safer and effective alternative to piperidine in Fmoc-SPPS.