Until recent decades, sickle cell disease (SCD) was associated with recurrent, disabling pain, organ failure and death in childhood or early adulthood. SCD treatment advances have now decreased pain and prolonged survival, but episodic or chronic pain may still require substantial analgesic use and frequent hospitalization for pain episodes. This pain is poorly characterized and often poorly treated. Adult patients may face barriers to comprehensive SCD care, stigmatization of their care-seeking behavior by providers and lack of family support, forcing them into maladaptive coping strategies. The Pain in Sickle Cell Epidemiology Study (PiSCES) attempts to develop and validate a biopsychosocial model of SCD pain, pain response and healthcare utilization in a large, multisite adult cohort. PiSCES participants complete a baseline survey and six months of daily pain diaries in which they record levels of SCD-related pain and related disability and distress as well as responses to pain (e.g., medication use, hospital visits). PiSCES will advance methods of measuring pain and pain response in SCD by better describing home-managed as well as provider-managed pain. PiSCES will assess the relative contributions of biological (disease-related), psychosocial and environmental (readiness to utilize) factors to overall pain and pain response in SCD, suggesting targets for biobehavioral interventions over time. Importantly, PiSCES will also identify "triggers" of SCD pain episodes and healthcare utilization in the moment of pain, suggesting targets for timely care that mutes pain episodes.