In this randomized, double-blind, parallel study of a group of 22 children and teenagers, prednisone efficacy in acute Sydenham’s chorea was assessed. Use of prednisone (2 mg/kg/day during 4 weeks, followed by a gradual discontinuation) in the 22 patients and in a placebo group (n = 15) was evaluated by a chorea intensity score based on presence, distribution, and interference of choreic movement on daily activities. Each patient was evaluated by the same pediatric neurologist weekly during the first month, followed by evaluation on weeks 8 and 12, with further evaluations as necessary if choreic movements persisted. Although initial chorea intensity was similar in both groups, a significant difference was observed after 1 week of medication (P < 0.001) with a larger reduction in the prednisone group, that continued until the end of the study. Percentage decrease in chorea intensity scale score also was persistently and significantly (P < 0.001) greater in the prednisone group. Chorea complete remission time with prednisone (mean 54.3 days) was significantly shorter (P < 0.001) when compared with the placebo group (mean 119.9 days). Seven patients presented recurrences, with no difference between groups (13.6% and 26.7% in the prednisone and placebo groups, respectively). Severe adverse events to prednisone were not observed.