Onychomycosis is a common disease with a significant negative impact on quality of life. While the disease is usually manageable in general practice, a proportion of patients need specialist treatment in academic hospital clinics. However, it is an unknown question whether the incidence in those needing specialist treatments is changing. Furthermore, the comorbidity burden in this patient population severely affected by onychomycosis has never been characterized. We conducted a retrospective study on patients treated for onychomycosis in Danish hospitals from 1994 to 2018. The cohort was observed for 24 years, and the data comprise 7.2 million Danes and their hospital diagnoses. A disease trajectory algorithm was used to examine the comorbidity burden in the cohort. A total of 2,271 patients received hospital treatment for onychomycosis during the time period, of which 1358 (59.8%) were men. The data show an increase in the incidence of hospital-treated cases since 2012 and that the most common comorbidities in this patient population include cardiovascular disease, alcohol-related diagnoses, and diabetes. One explanation of the increase in specialist treatment may include a general increase in patients with decreased resilience to fungal disease. This lack of resilience may both include an increasing elderly population with atherosclerosis, diabetes, and immunosuppression but also a potential increase in patients treated with immunosuppressive agents. Another possible explanation may include a shift in patient expectations in the case of treatment failure. Thus, patients may have an increasing demand for specialist treatment. While our data document an increase in the number of patients in need of specialist treatment for onychomycosis, we suggest future research to examine the general incidence of onychomycosis but also whether this increase in an apparently recalcitrant disease may be attributed to increased antifungal resistance, more specialist treatment options, or increased attention to dermatomycoses.