Sickle cell disease (SCD), an inherited group of blood disorders, is a major public health problem worldwide. Patients experience severe anemia, increased risk of life-threatening infections, painful crisis, and chronic organ damage. Access to comprehensive care for SCD is known to improve outcomes; however, it is only reported from large urban centers serving one metropolitan area. Alabama, US, is a largely rural state with a significant number of children born each year with SCD. Prior to the development of our regional clinic network, the Children and Youth Sickle Network (CYSNSM), 50% of patients identified by newborn screening were not enrolled in comprehensive sickle cell care. The majority of non-enrolled patients lived in southern Alabama. Rural areas in this region are particularly plagued by poverty and poor access to healthcare. Life expectancy is equivalent to residents of Sri Lanka. This area has 15.7 doctors/10 000 residents compared with the statewide ratio of 41.9 doctors/10 000 residents.To improve access to care, a regional clinic network, the CYSNSM, was established in 1995. This paper reviews the impact of the CYSNSMon pediatric SCD in Alabama over the first 5 years of implementation.Since its inception in 1995, the CYSNSMhas provided care for 923 patients compared with 450 prior to the development of the clinic network. Currently, 90% of all cases identified by newborn screening are enrolled compared with 50% pre-CYSNSM. Prior to the network, the average age of patients at their first clinic visit was 21 months. In the post-CYSNSMperiod, the average age at first clinic visit decreased substantially to 5.3 months. Prior to the CYSNSM, patients traveled on average 90 miles to a comprehensive clinic. Post-CYSNSM, this distance has been cut in half to an average of 45 miles. A total of 70% of patients now live within 30 miles of a clinic. Most importantly, the infection death rate has decreased from 5.71 deaths/100 patient years to 1.94 deaths/100 patient years.The development, implementation, and evaluation of the CYSNSMshow that comprehensive care delivery in a rural setting is feasible and improves outcomes in pediatric SCD.