6567 Background: Response to therapy prolongs survival in patients with myelodysplastic syndromes (MDS). The aim of this study is to evaluate the impact of complete cytogenetic response (CCyR) on survival in patients with MDS and abnormal cytogenetics. Methods: We reviewed 2311 consecutive patients with MDS and cytogenetic abnormalities who were treated at our institution from 2006 to 2023. Results: CCyR was observed in 330 patients (14%), complete response (CR) in 208 (9%), CR with bilineage recovery (CRbi) in 255 (11%), CR with unilineage recovery (CRuni) in 151 (7%), CR with incomplete hematologic recovery (CRh) in 4 (0.2%), and non-CR in 1363 (59%). With a median follow-up of 59 months, the median overall survival (mOS) was 14 months. Ten months for non-CR, 19 months for CRh/CRbi/CRuni, 21 months for CR, and 26 months for patients with CCyR (p < 0.001). With stem cell transplant (SCT) censoring, mOS was 15 months. Eleven months in non-CR, 19 months in CRh/CRbi/CRuni, 19 months in CR, and 27 months for patients with CCyR (p < 0.001). In low-risk MDS by the International Prognostic Scoring System (IPSS), mOS with SCT censoring was 87 months for CCyR, compared to 40 months for non-CR, 38 months for CRh/CRbi/CRuni, and 36 months for CR (p < 0.001). In intermediate/high-risk MDS mOS with SCT censoring mOS was 25 months in CCyR, compared to 9 months in non-CR, 15 months in CRh/CRbi/CRuni, and 17 months in CR (p < 0.001). In a multivariate regression analysis, age > 75 years (HR 3.1, p < 0.001), complex karyotype (HR 2.15, p < 0.001) performance status 3-4 (HR 1.48, p < 0.001), hemoglobin < 8 g/dL (HR 1.48, p=0.003), creatinine > 1.3 g/dL (HR 1.44, p < 0.001), therapy-related AML (HR 1.41, p < 0.001), infection at diagnosis (HR 1.34, p =0.003), white blood cells > 50 x109/L (HR 1.31, p <0.001), cardiac comorbidities (HR 1.26, p < 0.001), platelets < 20 x109/L (HR 1.26, p=0.001), pneumonia at diagnosis (1.22, p =0.006), and core-binding factor cytogenetics (HR 0.48, p < 0.001) were independently prognostic for survival in this select group. Conclusions: Achievement of CCyR in patients with MDS and abnormal cytogenetic abnormalities leads to improved survival. Given poor outcomes in older patients with MDS, CCyR can be used as a valid surrogate for long-term outcomes.