OBJECTIVE： To investigate clinical efficacy and adverse reactions （ADRs） of 4 kinds of the second-generation antipsychotic drugs in the treatment of acute phase of schizophrenia. METHODS： 159 patients with schizophrenia were randomly divided into risperidone group （40 cases）， olanzapine group （40 cases）， aripiprazole group （39 cases） and ziprasidone group （40 cases）. All groups were given routine dosage of relevant medicine by routine usage for 6 weeks. Mental status of patients were measured by PANSS before treatment and after 2， 4 and 6 weeks of treatment. At the same time， blood glucose， blood lipid， prolaction and other metabolic and biological indicators were all detected. RSESE， BARS and UKU were adopted to evaluate ADR. RESULTS： A total of 100 patients completed the study. Compared with aripiprazole group and ziprasidone group， risperidone and olanzapine inhibited symptom more rapidly， with statistical significance （P＜0.05）. After treatment， body mass index and abdominal circumference of olanzapine group were significantly higher than those of other 3 groups， with statistical significance （P＜0.05）. Low density lipoprotein of olanzapine group was increased significantly， there was statistical significance compared to ziprasidone group and aripiprazole group （P＜0.05）. Prolactin level of risperidone group was significantly higher than those of other 3 groups， while that of aripiprazole group was significantly lower than those of other 3 groups， with statistical significance （P＜0.05）. ADRs of 4 drugs were mild or moderate， most of whom could be alleviated by symptomatic treatment. CONCLUSIONS： In the treatment of acute phase schizophrenia， 4 drugs of the second-generation have similar curative effect in symptoms control， among which risperidone and olanzapine inhibit positive symptom more rapidly while more ADRs that related to lipid and glucose metabolism and prolactin also show. Aripiprazole and ziprasidone induce less ADRs relatively， and patients show better tolerability. Physicians should consider all kinds of factors in drugs selection， and make individualized treatment plan.