A study of 1000 patients with essential thrombocythemia (ET) treated at the Center for Research and Innovation in Myeloproliferative Neoplasms (CRIMM) in Florence, Italy, between 1980 and 2023, provides insights into the clinical features, risk factors, and outcomes of ET. The median age was 59 years, with 65% female patients. JAK2, CALR, and MPL mutations were present in 66%, 19%, and 4% of patients, respectively, with 11% being triple-negative (TN). Extreme thrombocytosis and leukocytosis were present in 16% and 16% of patients, respectively, and 52% had at least one cardiovascular risk factor. JAK2-mutated patients were older, while CALR and TN patients were younger. Female patients were more likely to have TN or JAK2 mutations than CALR mutations. Excessive thrombocytosis was associated with CALR, TN, and MPL mutations, while leukocytosis was linked to JAK2 mutations. Multivariate analysis showed that age ≥60 years and JAK2 mutation were significant risk factors for arterial thrombosis-free survival, while JAK2 mutation was a risk factor for venous thrombosis-free survival. Older age, male gender, and high neutrophil counts were significant risk factors for overall survival. CALR and MPL mutations were associated with higher risk of myelofibrosis progression. Cytoreductive therapy was associated with reduced risk of venous and arterial thrombosis. The study highlights the importance of risk stratification and treatment strategies in managing ET. The findings provide valuable data for understanding ET and planning future studies.A study of 1000 patients with essential thrombocythemia (ET) treated at the Center for Research and Innovation in Myeloproliferative Neoplasms (CRIMM) in Florence, Italy, between 1980 and 2023, provides insights into the clinical features, risk factors, and outcomes of ET. The median age was 59 years, with 65% female patients. JAK2, CALR, and MPL mutations were present in 66%, 19%, and 4% of patients, respectively, with 11% being triple-negative (TN). Extreme thrombocytosis and leukocytosis were present in 16% and 16% of patients, respectively, and 52% had at least one cardiovascular risk factor. JAK2-mutated patients were older, while CALR and TN patients were younger. Female patients were more likely to have TN or JAK2 mutations than CALR mutations. Excessive thrombocytosis was associated with CALR, TN, and MPL mutations, while leukocytosis was linked to JAK2 mutations. Multivariate analysis showed that age ≥60 years and JAK2 mutation were significant risk factors for arterial thrombosis-free survival, while JAK2 mutation was a risk factor for venous thrombosis-free survival. Older age, male gender, and high neutrophil counts were significant risk factors for overall survival. CALR and MPL mutations were associated with higher risk of myelofibrosis progression. Cytoreductive therapy was associated with reduced risk of venous and arterial thrombosis. The study highlights the importance of risk stratification and treatment strategies in managing ET. The findings provide valuable data for understanding ET and planning future studies.