Objectives To compare the effectiveness of paliperidone and ziprasidone and its influence on prolactin in female bipolar disorder patients with manic episodes. Methods A total of 95 female bipolar patients with manic episodes admitted to Chongqing Three Gorges Central Hospital from January 2017 to July 2018 were selected. The patients were divided into paliperidone group（ n=50） and ziprasidone group（ n=45） by random number table method. Both groups were given lithium carbonate tablets， on the basis of which paricipanone and ziprasidone were administered separately for 6 weeks. The scores of Clinical Global Impression scale（ CGI） and the Young's Mania Rating Scale（ YMRS） of the two groups were evaluated， and changes in serum prolactin， doses of lithium carbonate， and adverse reactions were monitored. Results The total effective rates after treatment were 84.00%（ 42/50） and 88.89%（ 40/45）， and the difference was not statistically significant （χ2=0.479，P ＞ 0.05）. There was no group×time interaction for the YMRS scores in the two groups（ P ＞ 0.05）. There was group×time interaction for the serum prolactin in the two groups（ P ＜ 0.05）. There was no significant difference in the dose of lithium carbonate between the two groups（ P ＞ 0.05）. The incidence of hyperprolactinemia in the ziprasidone group（ 28.00%， 14/50） was lower than that in paliperidone group（ 6.67%， 3/45）， and the difference was statistically significant（ χ2=7.336，P＜ 0.05）. There was no significant difference in the incidence of extrapyramidal reaction， tachycardia， nausea and vomiting， and dizziness and headache （P＞ 0.05）. Conclusions The effectiveness of paliperidone and ziprasidone in the treatment of female bipolar disorder manic episodes is similar， but ziprasidone has less effect on serum prolactin and can reduce the incidence of hyperprolactinemia.