Extended interval dosing regimens of immune checkpoint inhibitors have been implemented widely. However, their approval was mainly based on pharmacokinetic modeling and simulations. Consequently, comparative safety data of extended interval dosing regimens in a real‐world setting are limited. This study compares grade ≥3 immune‐related adverse events between standard and extended interval dosing of nivolumab in patients with melanoma and explores associated risk factors. This retrospective cohort study included patients with melanoma treated with nivolumab monotherapy from April 2016–September 2021 in the MULTOMAB study. Data on baseline characteristics and immune‐related adverse events were collected from patients’ electronic medical records with a maximum follow‐up of 6 months. A total of 236 patients (125 metastatic and 111 adjuvant) were included, with 146 in the standard cohort and 90 in the extended interval cohort. Grade ≥3 immune‐related adverse events occurred in 20 patients: 13 (8.9%) patients in the standard cohort and 7 (7.8%) in the extended interval cohort. No significant differences in grade ≥3 immune‐related adverse events were observed between the two cohorts ( P = 0.763). This study suggests that the risk of severe immune‐related adverse events is comparable between both interval dosing regimens of nivolumab in patients with melanoma. Therefore, the extended interval dosing of nivolumab appears to be safe for application in standard care.