ABSTRACTAn increasing number of isolations ofCorynebacterium diphtheriaehas been observed in recent years in the archipelago of New Caledonia. We aimed to analyze the clinical and microbiological features of samples withC. diphtheriae. AllC. diphtheriaeisolates identified in New Caledonia from May 2015 to May 2019 were included. For each case, a retrospective consultation of the patient files was conducted. Antimicrobial susceptibility phenotypes,toxgene and diphtheria toxin expression, biovar, and the genomic sequence were determined. Core genome multilocus sequence typing (cgMLST), 7-gene MLST, and search of genes of interest were performed from genomic assemblies. Fifty-eight isolates were included, with a median age of patients of 28 years (range: 9 days to 78 years). Cutaneous origin accounted for 51 of 58 (87.9%) isolates, andC. diphtheriaewas associated withStaphylococcus aureusand/orStreptococcus pyogenesin three-quarters of cases. Half of cases came either from the main city Noumea (24%, 14/58) or from the sparsely populated island of Lifou (26%, 15/58). Sixtox-positive isolates were identified, associated with recent travel to Vanuatu; 5 of these cases were linked and cgMLST confirmed recent transmission. Two cases of endocarditis in young female patients with a history of rheumatic fever involvedtox-negative isolates. The 58 isolates were mostly susceptible to commonly used antibiotics. In particular, no isolate was resistant to the first-line molecules amoxicillin or erythromycin. Resistance to tetracycline was found in a genomic cluster of 17 (29%) isolates, 16 of which carried thetetOgene. There were 13 cgMLST sublineages, most of which were also observed in the neighboring country Australia. Cutaneous infections may harbor nontoxigenicC. diphtheriaeisolates, which circulate largely silently in nonspecific wounds. The possible introduction oftox-positive strains from a neighboring island illustrates that diphtheria surveillance should be maintained in New Caledonia, and that immunization in neighboring islands must be improved. Genomic sequencing uncovers how genotypes circulate locally and across neighboring countries.IMPORTANCEThe analysis ofC. diphtheriaefrom the tropical archipelago of New Caledonia revealed a high genetic diversity with sublineages that may be linked to Polynesia, Australia, or metropolitan France. Genomic typing allowed confirming or excluding suspected transmission events among cases and contacts. A highly prevalent tetracycline-resistant sublineage harboring thetetOgene was uncovered. Toxigenic isolates were observed from patients returning from Vanuatu, showing the importance of improving vaccination coverage in settings where it is insufficient. This study also illustrates the importance for diphtheria surveillance of the inclusion of isolates from cutaneous sources in addition to respiratory cases, in order to provide a more complete epidemiological picture of the diversity and transmission ofC. diphtheriae.