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Yeasts belonging to the Candida genus typically reside on the mucosal surface and within the respiratory and gastrointestinal tract as commensals. Under conditions of host vulnerability, they can act as opportunistic pathogens, leading to various forms of candidiasis, including candidemia. Such infections can be particularly problematic when caused by isolates that exhibit resistance to antifungal drugs, which are becoming more prevalent in many regions. One hundred and seven samples of Candida spp. were isolated from patients with candidemia in the hospital San Matteo in Pavia (Italy) over a period of 6 years, from 2015 to the first COVID wave in spring 2020. In order to understand the epidemiology of Candida infections in this hospital setting, the isolates were whole-genome sequenced, confirming that most belonged to C. parapsilosis and C. albicans. Comparative genomics revealed that isolates of C. albicans were genomically diverse, indicative of repeated introductions in the hospital from the community. C. parapsilosis isolates on the other hand belonged to two groups of highly similar isolates, representing strains capable of long-term persistence in the hospital. All isolates of the main persistent group were resistant to fluconazoleresulting from the Y132F substitution in ERG11 and the N455D substitution in UPC2, while presenting variable levels of resistance to voriconazole and itraconazole. Interestingly, with the exception of the single isolate susceptible to both voriconazole and itraconazole, all the 61 isolates presented one unreported missense mutation in MRR1 (S1907C).