Ipilimumab is approved for adjuvant melanoma treatment at a dose of 10 mg/kg, but its use is limited owing to high toxicity and treatment-associated costs. We retrospectively analyzed 29 patients who underwent complete resection of stage IIC–III melanoma and were treated with ipilimumab 3 mg/kg in an adjuvant setting. The aim was to assess development of adverse events (primary endpoint) and to evaluate survival outcomes (secondary endpoint) under adjuvant treatment with ipilimumab in a real-life setting. Immune-related adverse events (irAE) of all grades were reported in 72.4% of patients, grade 3 in 5.3% (n=2), and none for grade 4 or 5. Immune-related hypophysitis resolved in 3/8 (37.5%) and immune-related thyroiditis in 7/10 (70%) cases, whereas the others remained on substitution drugs. The rest irAEs affected the gut (n=8), skin (n=5), liver (n=2), and uvea (n=2) and resolved completely. Only one patient required tumor necrosis factor-α owing to grade 3 colitis. Hospitalization was required in five cases owing to irAE (four colitis and one hypophysitis). At a median follow-up of 9.7 (1.7–16.8) months, 65.5% of the patients were free of disease. Median progression-free survival was 15.1 months, and median overall survival was not reached yet. Ipilimumab 3 mg/kg for the adjuvant treatment of high-risk patients with fully resected melanoma favors a better safety profile compared with the approved dose of 10 mg/kg in the same setting. Although its limited application owing lately promising data of antiprogrammed cell death protein-1 treatment, it may be considered as additional option or second-line treatment after fully resected disease recurrence under antiprogrammed cell death protein-1 treatment.