Pediatric autoimmune hemolytic anemia (AIHA) is a heterogeneous disease with significant morbidity due to the underlying condition and its treatment. Evidence-based guidelines for evaluation and management are lacking. Data from 399 patients with AIHA followed at 15 pediatric centers were collected to identify factors associated with secondary diagnoses, recurrent/chronic course, therapeutic efficacy, and mortality. Most had AIHA associated with secondary diagnoses including Evans syndrome (142/385 [37%]), other autoimmunity (86/392 [22%]), and inborn errors of immunity (IEI; 68/379 [18%]). Of 305 patients tested, 82% had abnormal functional immune results. Genetic testing for IEI was performed in 109 of 348 patients (31%), with pathogenic findings identified in 32% of those tested. Patients with IEI or other autoimmunity more frequently had abnormal immunoglobulin and complement testing. Prevalence of IEI was not different between those presenting with and without infection. The median number of treatments for the first AIHA episode was 2 (range, 0-17). Of those with warm AIHA, 31% received steroid-sparing therapy during the first episode. Patients with recurrent AIHA (42%) had a higher rate of abnormal immune tests (odds ratio [OR], 2.29; P = .012), Evans syndrome (OR, 4.85; P< .001), IEI (OR, 3.88; P< .001), and other autoimmune disorders (OR, 3.29; P< .001). With a median follow-up of 4.9 years (range, 0-19.4), 72 of 257 (28%) with warm AIHA continued to have active disease on treatment. Of the 399 patients, 10 died, all of whom had secondary diagnoses. Expansive immune evaluation, monitoring, and targeted treatments directed at immune diagnoses are needed for pediatric AIHA, highlighting the need for evidence-based pediatric AIHA guidelines.