Introduction: A single institution case-control study was conducted to evaluate the risk of developing chronic myeloproliferative neoplasms (MPNs) associated with prior autoimmune disease and cardiovascular disease (CVD). Method: Cases were 323 MPN patients and controls were 333 chronic lymphocytic leukemia (CLL) patients. Odds ratios (ORs) and p-values using Fischer's exact tests were calculated. The data was adjusted for confounding effects by logistic regression. Results: A significantly increased risk of MPNs compared to CLL was observed in subjects with a prior history of any autoimmune disease (OR = 1.86, 95%CI 1.16-2.98). A positive association between JAK2-V617F positive MPN and any autoimmune disease was observed at follow-up (OR = 2.62, 95% CI 1.21-5.67). A significantly increased risk of MPN compared to CLL was also observed in subjects with prior thromboembolic events (TE-events) (OR = 2.09, 95%CI 1.42-3.08). In the MPN group, an increased risk of JAK2-V617F-positive disease was observed in subjects with prior TE-events (OR= 2.19, 95%CI 1.51-3.16). Discussion: It is discussed if chronic inflammation in relation to autoimmunity and atherosclerosis might elicit mutations in the hematopoietic stem cell resulting in MPNs, or whether this association actually reflects a long-lasting pre-MPN-diagnosis phase, in which the MPN-disease per se contributes to a chronic inflammatory state and immune deregulation. (C) 2015 Elsevier Ltd. All rights reserved.