Sickle cell disease (SCD) is characterized by vaso-occlusive crises (VOCs), resulting in acute and chronic pain, which have a significant impact on patients’ lives. The SWAY survey assessed the impact of SCD on patients. SWAY was a cross-sectional survey of SCD patients aged 6 and above and treating HCPs across 16 countries. Surveys were self-complete or proxy surveys assessing demographics, symptoms, VOC burden and impact on activities of daily living (ADLs) and finances. Patient were enrolled via treating HCPs and patient association groups. Here we report US patient data. The survey included 384 US SCD patients, 61% female, mean (SD) age 30.1 (13.4) years. Most patients (96%) experienced ≥1 VOC in the 12 months before survey completion (mean 7.1, SD 5.7); 59% experienced ≥5 VOCs. Of all VOCs, 52% resulted in overnight hospitalization, 22% were managed at home, 13% were treated in ER, 13% were treated by pharmacist, GP or specialist. Chronic pain was present on average 4.0 (SD 1.98) days per week. When rated on a 7-point scale (scores of 5-7 indicate ‘high impact’), 49% of patients reported a high negative impact of SCD on ADLs. Overall, 36% were on disability, 25% part/full-time employed, 24% unemployed, 12% students, 3% other. Employed patients reported a high impact on work, with 76% reducing hours and 58% been made to stop working. In the 7 days before survey completion, patients missed an average 7.3 (SD 10.56) hours’ work. A high degree of presenteeism (40.4%) and absenteeism (20.6%) was reported, in addition to a high overall work impact (50.2%). These data demonstrate SCD has a substantial impact on patients’ ADLs and ability to work. Furthermore, VOCs frequently resulted in hospitalizations demonstrating wider economic burden. Improved SCD management would enhance patients’ quality of life at home and work with wider positive economic effects.