Inclusion Criteria:  Men with confirmed diagnosis of HbSS or Hb beta zero thalassemia Ages between 18 to 40 years Eligible study participants must receive care in an SCD clinic at AKTH and MMSH at the time of the recruitment Participants must commit to long-term follow-up and taking the trial medications At least 3 episodes of priapism, each lasting for no less than an hour in the past 6 months. Adequate renal and hepatic function (baseline liver enzymes and synthetic activities should be no more than four-fold above the reference ranges for Aminu Kano Teaching Hospital (AKTH). These are the ranges obtained in AKTH: Alkaline phosphatase: 42-110 U/L, Alanine transaminase: 4-34 U/L, Aspartate transaminase: 7-45 U/L, Albumin: 32-52 g/L, and Globulin: 32-43 g/L.  Exclusion Criteria:  Individuals already enrolled in another clinical trial eGFR <50ml/min Liver cirrhosis based on clinical history, laboratory data or both Previously known pulmonary hypertension based on TRJV greater than 3.0 m/sec Contraindications to tadalafil (arrhythmia, severe liver disease, concurrent use of nitrates, etc.) or hydroxyurea (leg ulcer, hypersensitivity, etc.). Patients who have penile prosthetic implants or shunts or any other surgical procedure on the penis Patients who have taken drugs/medications that may induce priapism over the 14 weeks before trial: Medications injected directly into the penis to treat erectile dysfunction, such as alprostadil, papaverine, phentolamine, and others Antidepressants, such as fluoxetine, bupropion, and sertraline Alpha blockers including prazosin, terazosin, doxazosin, and tamsulosin Medications used to treat anxiety or psychotic disorders, such as hydroxyzine, risperidone, olanzapine, lithium, clozapine, chlorpromazine, and thioridazine Blood thinners, such as warfarin and heparin Hormones such as testosterone or gonadotropin-releasing hormone Medications used to treat attention-deficit/hyperactivity disorder (ADHD), such as atomoxetine (Strattera) Alcohol, marijuana, cocaine and other illicit drug abuse can cause priapism Not able to understand or comply with study instructions and requirements