Objective To determine the clinical efficacy and safety of magnesium valproate sustained release tablets and combination with quetiapine in treatment of manic episode in the elderly with bipolar disorder. Methods A total of 46 elderly patients (aged 60 to 78 years) who met the criteria of the International Classification of Diseases (ICD-10) for manic episode of bipolar disorder admitted in our hospital from May 2013 to May 2014 were enrolled in this study. They were randomly assigned to 2 groups, and treated with magnesium valproate sustained release tablets (control group) or combined with quetiapine (study group). In 6 weeks after treatment, Bech-Rafaelsen Mania Rating Scale (BRMS) and Treatment Emergent Symptoms Scale (TESS) were employed to evaluate the clinical efficacy and adverse effects respectively. Results BRMS scores were dropped significantly in both groups (P＜0.05). At the end of the second weeks, there were significant differences in the total score of BRMS and the factor points (noisy/speech, sleep) between the study and control groups (P＜0.05). At the end of 6 weeks’ treatment, there was no significant difference in the total score of BRMS between the 2 groups (P＞0.05). No severe adverse effect was seen in the both groups, and there was no significant difference in TESS score between them. Conclusion Magnesium valproate sustained release tablets combined with quetiapine show better efficacy and sound safety in the treatment of maniac episode in the elderly patients, especially in controlling excitement symptoms and improving sleep at the early stage of treatment (the end of 2 weeks).