• Patients who have been diagnosed with essential thrombocythemia or polycythemia vera by World Health Organization 2016 diagnostic criteria.

• Patients with essential thrombocythemia must be very low (no history of thrombosis, age \<60, and no JAK2 mutation), low (no history of thrombosis, age \<60, presence of JAK2 mutation), or intermediate risk (no history of thrombosis, age \>60, no JAK2 mutation) by IPSET criteria. Patients with polycythemia vera must be low risk (no history of thrombosis and age \<60) by NCCN guidelines.

• Patients with an MPN-SAF TSS (MPN-10) score \>10 AND at least one individual feature \>5 documented on a separate visit within 3 months prior to study registration, as documented in the clinical record or obtained by clinician. If not previously documented in the electronic medical record, participants must be blinded to purpose of MPN SAF TSS scoring for eligibility determination. Average daily MPN-SAF TSS (MPN-10) score must remain \>10 with any individual feature \>5 for the week-long baseline assessment prior to ruxolitinib initiation.

• Patients who have previously received or are receiving cytoreductive therapy (i.e. hydroxyurea, anagrelide, interferon) are eligible for the study if therapy was used for the indication of symptom control, or if therapy was used for pre-operative control of blood counts. If a subject is still receiving cytoreductive therapy at the time of screening and enrollment, there will be a wash-out period from prior cytoreductive therapy at least 7 days prior to ruxolitinib initiation.

• Age ≥18 years.

• ECOG performance status ≤2 (Karnofsky ≥60%)

• Participants must have adequate organ and marrow function as defined below:

‣ leukocytes ≥3,000/mcL

⁃ absolute neutrophil count ≥1,500/mcL

⁃ platelets ≥100,000/mcL

⁃ total bilirubin ≤ institutional upper limit of normal (ULN)

⁃ AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN

⁃ creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2

• Participants with a prior or concurrent malignancy not receiving treatment for concurrent cancer diagnosis and/or prior concurrent malignancy within 5 years except for basal cell carcinoma or squamous cell carcinoma of the skin.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

• For participants with evidence of chronic human immunodeficiency virus (HIV) infection, they must be negative for HBV DNA, HCV RNA, or hepatitis B surface antigen (BsAg) on suppressive therapy, if indicated.

• Participants must be previously vaccinated with the Herpes Zoster (Shingles) vaccine or must be willing to start prophylactic Acyclovir 400 mg twice daily (BID) or suitable alternative for duration of treatment with ruxolitinib.

• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.

• Ability to understand and the willingness to sign a written informed consent document.