Background: MDS are heterogeneous clonal disorders of hematopoietic stem cells. MDS with isolated deletion 5q is the most distinct group of MDS, comprises 3-4.5% of MDS cases in Latin America and seems to have a favorable prognosis, with a lower risk of progressing to AML and longer overall survival (OS). Some factors have been associated with a poor prognosis, such as dysgranulopoiesis, age over 70 years, transfusion dependency and TP53 mutation. This study aims to describe clinical, laboratory and outcome of patients with MDS with isolated del(5q) in South America. Methods: We retrospectively reviewed patients with MDS with isolated del(5q) who met WHO 2016 criteria from 4 Brazilian (1 in the Northeast and 3 in the Southeast) diagnosed between 1999 and 2019 and from 4 Argentinean centers diagnosed between 2003 and 2019. OS and leukemia progression were estimated using the Kaplan-Meier method. Cox model was built as progression model. All variables with a p-value lower than 0.05 were included in the final multivariate model. Results: Fifty-eight patients (16 Argentinean and 42 Brazilian) included met the eligibility criteria with median age of 67.3 (61-75) years old, predominance of females (71%) and transfusion dependency in 60% of patients. At diagnosis, median Hb level was 8.0 (3.5-17.6) g/dL, and macrocytosis, thrombocytosis and neutropenia were present in 52%, 28% and 45% of patients, respectively. Bone marrow (BM) trephine was predominantly hypercellular (43%). Dysplasia >1 lineage was found in 33 (57%) patients and 22 (38%) had > 2% of blasts in BM aspirate. Fibrosis greater than grade 1 was observed in 7% (4/34 samples). The deletion 5q was isolated in 66%. p53>1% by immunohistochemistry was found in 26% (5/19 BM studies at diagnosis) and only one patient (from 18 samples) showed del17p by FISH. Most patients were treated with ESA, 17 received lenalidomide and 15 thalidomide (only Brazilian). With a median follow-up of 7.6 (range 3.2-10.5) years, 57% died including 6 related to AML progression and one patient with concomitant AML and DLBC Lymphoma. The median OS was 43.2 (36-78) months and to AML progression of 6.9 (range, 6.5-7.3) years; OS estimated at 8 years was 18%. Univariate analysis showed that age > 67 years old, ECOG ≥ 2, percentage of BM blasts > 2% and fibrosis in BM biopsy > 1 were associated with lower OS, while lenalidomide treatment was the only factor associated with its improvement. Multivariate analysis confirmed that ECOG ≥ 2 (HR 6.88 [CI95% 2.25 – 21.09], p ≤ 0.001), > 2% of BM blasts (HR 3.66 [CI95% 1.09 – 12.30], p = 0.04) and lenalidomide treatment (HR 0.31 [CI95% 0.12-0.80], p = 0.016) were associated with OS. Conclusion: Median OS of patients with isolated deletion 5q MDS seems slightly lower in this South American series when compared to previously published data. Some factors that can be easily assessed at diagnosis as performance status and the percentage of BM blasts are associated with to prognosis. And, the use of lenalidomide was associated with a better outcome, with a heterogeneity of access among patients due to the retrospective characteristic of the study. There is also a need to detect TP53 by detection by immunohistochemistry, molecular biology and FISH, which is not routinely available in South American centers.