Introduction: Plasmids are involved in the dissemination of antimicrobial resistance (AMR) and as virulence factors in microbes, however, total plasmid content (the plasmidome) remains unexplored by metagenomics and its role in bronchiectasis unclear. Methods: Sputum samples (n=251) from patients with stable bronchiectasis were prospectively collected across four countries (Singapore, Malaysia, Scotland, and Italy) and subjected to shotgun metagenomic sequencing. Contigs of plasmid origin were identified using PlasForest and plasmid identity determined by BLAST homology against a PLSDB plasmid database. AMR, virulence, and toxins were subsequently evaluated with PathoFact. Differentially adundant plasmids were determined using Linear discriminant analysis Effect Size. Results: The plasmidome in bronchiectasis associates with diverse AMR, virulence, and toxin genes. Plasmidome composition significantly differs across countries (p<0.01) and in frequent exacerbators (p<0.05) irrespective of geographic origin. Differentially abundant plasmids associated with frequent exacerbators include those isolated from Pseudomonas spp. (44%) and Klebsiella spp. (11%) which harbour resistance to macrolide-lincosamide-streptogramin (MLS) antibiotics, and exhibit significantly increased virulence (p<0.05). Conclusion: Plasmidome signatures associate with frequent exacerbator status in bronchiectasis independent of geographic origin. The plasmidome presents a novel opportunity for endophenotyping bronchiectasis, demonstrating clinical relevance particularly in informing antibiotic use. Funding: This research is supported by the Singapore Ministry of Health's NMRC under its Clinician Scientist Award (MOH-000710) (S.H.C).