Background: In patients suffering from bipolar disorders (BPD), we explored to what extent oral loading of sodium valproate (SV) leads to more rapid symptom improvement compared to intravenous loading and oral maintenance administration. Methods: Ninety patients (mean age: 35.00 years) with BPD and currently in an acute manic state were randomly assigned to one of three study conditions: oral loading (20 mg/kg oral single-dose SV on the first day, then 10-15 mg/kg SV daily, divided dose), intravenous loading (20 mg/kg SV intravenous injection on the first day, then 10-15 mg/kg orally, divided dose), or oral maintenance administration (15-20 mg/kg SV daily from the beginning) over the first 7 days of treatment. SV plasma levels, side effects and symptoms were evaluated at baseline and on days 1, 3, and 7 after commencing treatment. Results: There were significant Time-by-Group interactions for symptom improvements, symptom severity, and SV plasma levels, with positive values in the oral and intravenous loading conditions, compared to the oral maintenance condition. Post hoc analyses showed that oral and intravenous conditions led to similar improvements. Conclusions: Both oral and intravenous loading of SV led to quicker and more efficient improvement and SV plasma levels as compared to an oral maintenance regimen.