Vaso-occlusive episodes (VOE) are the most common complication resulting from sickle cell disease (SCD) in adults. VOEs are caused by ischemic tissue injury as a result of occlusion of microvascular beds from abnormal sickle shaped red blood cells (RBCs). Individuals with SCD display a host of complications associated with micro and occasionally macro vascular occlusion, including stroke, leg ulcers, spontaneous miscarriage, and renal insufficiency. The acute pain crisis is the most common reason patients with SCD seek medical care in emergency departments (EDs). Due to the recurrent nature of acute pain crises, possible inadequate knowledge of health care providers about the disease, and the intensity of treatment needed, patients with VOEs may be undermedicated in the ED. This can lead to low patient satisfaction, low provider satisfaction, and increased cost of care. Through the use of an ED observation unit (OU) or clinical pathway, patients experiencing VOEs can be effectively managed to improve outcomes, improve satisfaction, and decrease cost of care.