Purpose: To identify trends in physician drug prescribing practices for sickle cell disease (SCD). Methods: We used data from the National Disease and Therapeutic Index to evaluate medications prescribed to children (definition: aged 19 years or younger) and adults (20 years or older) with SCD by office-based physicians in the United States during 1997 to 2017. Prescriptions were evaluated in 3-year intervals. Results: The proportion of SCD visits that included new/continued hydroxyurea prescriptions increased from less than or equal to 8% before 2009 to 33% in 2015 to 2017. The increase was significant in visits by children (2.5% in 1997-1999 to 47% in 2015-2017; P =.003 by Spearman's rank-order correlation) but not in adults (6.9% to 11%; P =.12). Opioids, started/continued in 13% (lowest 3-year average) to 35% (highest) of visits by children and 55% to 81% of visits by adults, remained the most frequently prescribed medications for SCD overall. There were no significant changes over time in opioid prescribing for adults (P =.64) or children (P =.38). Hematologists/oncologists accounted for a higher proportion of visits by children (67.2% over 1997-2017) than adults (25.2%), while emergency medicine visits were higher in adults (14.0%) than children (2.6%). Conclusions: This study suggests a robust increase in hydroxyurea prescribing for children with SCD. The BABY HUG trial, which demonstrated safety and efficacy of starting hydroxyurea in infancy and informed current SCD guidelines recommending broader use in children, may have contributed to this increase. However, hydroxyurea prescribing for adults remains infrequent and considerably lower than opioids. Barriers in access to specialist care persist for adults with SCD.