Myelofibrosis (MF) is a clonal hematopoietic malignancy characterized by constitutional and localized symptoms, progressive splenomegaly, bone marrow fibrosis, and cytopenias. Although MF is well studied, few studies exist regarding its symptomatic burden in routine clinical practice. This study aimed to characterize symptoms and other clinical features of MF among patients in the United States. We conducted a retrospective medical record review of adult patients with an MF diagnosis between 1 January 2005 and 31 March 2010, stratified by the presence of palpable splenomegaly. Eligible patients had 12 months or more of follow-up after diagnosis (or after detection of splenomegaly, if present) unless death occurred. Demographic and clinical characteristics, MF-related symptoms, and treatments were reported by treating physicians. We report on 180 MF patients: 102 with splenomegaly, 78 without. Median age was 66 years, 63% were male, and 82% had intermediate-2 or high-risk MF (International Prognostic Scoring System). Fatigue was reported by ~85% of patients; weight loss, night sweats, and fever (any grade) were each reported by 50% or more of patients. Generalized abdominal pain, left subcostal pain, and early satiety occurred more frequently among patients with splenomegaly. Multiple symptoms were reported by 95% of patients. Common comorbidities were hypertension, diabetes, and chronic pulmonary disease. Symptoms are common in MF patients, regardless of the presence of palpable splenomegaly. Careful assessment of symptom burden is an important aspect of the clinical evaluation of patients with MF.