We examined the usability of smartphones for accessing a web-based e-Diary for self-monitoring symptoms in children and adolescents with sickle cell disease (SCD). One group of participants (n = 10; mean age, 13.1 ± 2.4 y; 5 M; 5 F) responded to questions using precompleted paper-based measures. A second group (n = 21; mean age, 13.4 ± 2.4 y; 10 M; 11 F) responded based on pain and symptoms they experienced over the previous 12 hours. The e-Diary was completed with at least 80% accuracy when compared to paper-based measures. Symptoms experienced over the previous 12 hours included feeling tired (33.3%), headache (28.6%), coughing (23.8%), lack of energy/fatigue (19.0%), yellowing of the eyes (19.0%), pallor (19.0%), irritability (19.0%), stiffness in joints (19.0%), general weakness (14.3%), and pain (14.3%), rating on average as 2.0 ± 1.7 (on 0 to 10 scale). Overall, sleep was good (8.1 ± 1.4 on the 0 to 10 scale). In conclusion, children with SCD were able to use smartphones to access a web-based e-Diary for reporting pain and symptoms. Smartphones may improve self-reporting of symptoms and communication between patients and their health care providers, who may consequently be able to improve pain and symptom management in children and adolescents with SCD in a timely manner.