This study aimed to evaluate the medical and socioeconomic impacts of IRDs using the nationwide health database and a large hospital-based cohort. This retrospective cross-sectional cohort study used data from the nationwide National Health Insurance Research Database (NHIRD). All patients with IRD from January 2012 to December 2016 were selected from the NHIRD and matched with the general population at a ratio of 1:4. All variables, including comorbidities, medications, service utilization, and medical costs, within 1 year from the date of the IRD diagnosis, were analyzed. Disability data were retrieved from the Taiwan Inherited retinal degeneration Project (TIP), a medical center-based database. A total of 4447 and 17,788 subjects from the nationwide database were included in the IRD and control groups, respectively. The Charlson comorbidity index score was higher in the IRD group (0.74:0.52, p < 0.001). Yearly visits to the ophthalmology clinic were more frequent in the IRD group (6.80:1.06, p < 0.001), particularly to tertiary medical centers (p < 0.001). The IRD group showed greater odds ratios (OR) for metabolic syndrome-related comorbidities, including hypertension (OR = 1.18, 95% confidence interval (CI) 1.10 to 1.26) and diabetes (OR = 1.32, 95% CI 1.21 to 1.45), and double the average yearly medical cost (2104.3 vs. 1084.6 USD, p < 0.001) and ten times the yearly ophthalmology cost (369.1 vs. 36.1 USD, p < 0.001). The average disability level was 54.17% for all subjects. This study revealed the large medical and socioeconomic impacts of IRD on not only patients with IRD, but also their family members and the whole society.