Background <p>Nocardiae are ubiquitous environmental soil pathogens that primarily cause invasive infections by inhalation or direct skin inoculation in immunocompromised patients. This multi-year population-based study compared epidemiological and clinical features of all cases diagnosed in our region.</p> Methods <p>Patients were enrolled in our large integrated healthcare region with culture-proven nocardiosis between 2010 and 2021. Clinical chart reviews were conducted to determine the clinical manifestations, risk factors, treatment and mortality including survival analysis.</p> Results <p>Ninety-four adults had a mean age of 61 ± 17 years. More cases occurred in males (57%) than females (43%). 96% of cases had underlying co-morbidities including diabetes, liver or renal failure, malignancy, transplant recipients, chronic lung disease, rheumatologic disease, or other inflammatory conditions. Pulmonary (53%) or skin and soft tissue infections (SSTIs) (30%) commonly occurred with infrequent diagnoses of central nervous system infection (CNS) (7%), bloodstream infection (BSI) (6%), and septic arthritis or intra-abdominal infection (IAI) (6%). Diverse <i>Nocardia</i> spp. were isolated, but 3 species complexes caused most cases [56/94 (60%)] including <i>Nocardia farcinica</i> (<i>n</i> = 21, 22.3%), <i>Nocardia cyriacigeorgica</i> (<i>n</i> = 16, 17%) and <i>Nocardia nova</i> (<i>n</i> = 19, 20.2%). Clinical presentation was not unique for individual <i>Nocardia</i> spp. infections. Overall mortality was 17.6% with a 1-year mortality of 13.2%. Delayed diagnosis (≥ 30 d) from symptom onset had higher mortality. A trend towards increased mortality occurred for <i>N. farcinica</i> &gt; <i>N. cyriacigeorgica</i> &gt; <i>N. nova</i> complex infections.</p> Conclusions <p>Prompt diagnosis of nocardiosis improves patient outcomes. Nocardia species-level identification predicts mortality for major species complexes causing nocardiosis in our region.</p> Clinica trial number <p>Not applicable.</p>