In response to the ongoing threat of hospital-acquired infections, we implemented a streamlined whole-genome sequencing program at Wellington Regional Hospital, using Oxford Nanopore Technologies long-read sequencing. Focusing on hospital-associated pathogens, we prospectively sequenced cultured isolates from inpatients using the MinION device. After each sequencing run, multi-locus sequence type data are cross-referenced with patient bed movement data from the hospital electronic data warehouse, which captures the precise timing of all inpatient bed movements. Between February and October 2022, 60 Clostridioides difficile isolates from inpatients were successfully sequenced, revealing sequence type (ST)2 as the predominant sequence type (12 cases) with higher exposure in Ward B. No substantial increase in overall cases beyond the hospital baseline variations was observed, indicating multiple introductions of ST2 into Ward B (confirmed later with phylogenetic analyses). In June 2023, a suspected transmission in the Neonatal Intensive Care Unit (NICU) involved two neonates identified with Methicillin-resistant Staphylococcus aureus (MRSA) ST97. Subsequent investigations detected 11 ST97 cases. Retrospective phylogenomic analyses, incorporating publicly available sequence data and data from New Zealand’s National Reference Laboratory, uncovered the longstanding presence of this MRSA ST97 lineage in the community since the late 1990s. Implementing nanopore sequencing has enabled real-time on-site monitoring of specific lineage incidences according to patients’ recent ward exposures, allowing early remedial action. Post-intervention, only two additional cases of C. difficile ST2 associated with Ward B exposure and a single case of S. aureus ST97 from a neonate in the NICU (unrelated to the initial outbreak) have been reported to date.