LL37, a human cathelecidin antimicrobial peptide comprising of 37 amino acids has emerged as one of the vital therapeutic peptides associated with a number of biological applications. In this context, we herein report a highly efficient and optimized methodology for the syn-thesis of LL37 through SPPS assisted by microwave power. Standard conditions employing uronium coupling reagents was unsatisfactory from the 20th amino acid residue onwards. A segmentation approach revealed that the amide bond formation between the Val and Ile was identified as the problematic coupling. It was found that DIC/Oxyma-Pure in conjunction with THF as the solvent gave best results during manual coupling of 20th position Ile and required double coupling as revealed by HPLC and MALDI-TOF MS. In order to verify the synthesis, anti-bacterial testing was carried out and the results revealed comparable values with that of literature reported. Keywords LL37 Á SPPS Á Microwave Á DIC Á OxymaPure Á THF Abbreviations DCC N,N 0 -Dicyclohexylcarbodiimide DIC N,N 0 -Diisopropylcarbodiimide DIPEA N,N-Diisopropylethylamine DMF N,N-Dimethylformamide HATU 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxidhexafluorophosphate HBTU N-[(1H-Benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide HOBt 1-Hydroxybenzotriazole PyBOP (Benzotriazol-1-yloxy) tripyrrolidinophosphonium hexafluorophosphate TFA Trifluoroacetic acid THF Tetrahydrofuran Electronic supplementary material The online version of this article (