Background: Ipilimumab, a fully human monoclonal Ab directed against the CTLA-4 receptor on T-cells, has shown significant improvement in OS for patients with metastatic melanoma in randomized phase III trials. Eosinophilia in peripheral blood of those patients has been observed, but its clinical significance as a prognostic factor has not been assessed. Methods: We report on a retrospective multi-center analysis of 123 patients who received ipilimumab in three centers between 2010 and 2013. Patients treated had AJCC unresectable stage III or stage IV melanoma of any origin and received ipilimumab in first- and second-line setting at the approved standard dosage of 3mg/kg (4 times q21d). Four patients were excluded due to missing baseline values in eosinophil count (EC). Results: Median OS for patients in final analysis (n=119) was 9.57 months. Based on cut-offs assessed by ROC curves, OS was estimated by Kaplan-Meier curves. Baseline absolute eosinophil count (AEC) ≥ 0.1 (10⁹/l) was significantly associated with improved OS (p= 0.002) with 6-, 12- and 18-month survival rates of 79%, 60% and 48% compared to rates of 48%, 37% and 19% for pts with baseline AEC below 0.1. Baseline relative eosinophil counts (REC) of ≥ 1.75% showed an even stronger significance (p<0.0001) with 6-, 12- and 18-months survival rates of 79% vs. 52%, 60% vs. 40% and 51% vs. 17.1% respectively. Conclusions: This retrospective analysis elucidates the possible association of baseline EC with OS of patients treated with Ipilimumab. Improvement of OS was highly significant in both analyses considering AEC (p= 0.002) and REC (p<0.0001). Since easily detectable biomarkers could be of great potential value, further effort on understanding the potential role of eosinophil granulocytes as possible effector cells in the immune-mediated response to anti CTLA-4 abs should be undertaken.