Objective Many antipsychotic drugs have cardiac side effects due to their pharmacological actions. Heart rate variability (HRV) analysis can be used as a potential indicator of cardiotoxicity in cases where a decrease in HRV occurs after the administration of antipsychotics such as clozapine. The purpose of this study was to explore the effects of 6 antipsychotic drug regimens on short-term HRV in patients with schizophrenia. Methods Data from 164 patients with schizophrenia between January 2018 and June 2023 were retrospectively analysed. Based on the drug used for treatment, the patients were categorised into clozapine combination (clozapine combined with aripiprazole, risperidone or ziprasidone), clozapine alone, olanzapine, aripiprazole, ziprasidone or risperidone groups. Heart rate variability indices were calculated using time domain analysis, including the standard deviation of the RR intervals (SDNN), the root mean square of successive RR interval differences (RMSSD) and the percentage of successive RR intervals over 50 ms (PNN50). Results Compared with the pretreatment period, the SDNN, RMSSD and PNN50 were significantly lower in the clozapine combination, clozapine, olanzapine and aripiprazole groups at the end of weeks 2 and 4 of treatment ( P < 0.05). However, these indicators in ziprasidone and risperidone groups did not show this significant decrease ( P > 0.05). Conclusion The effects of clozapine combination and clozapine on HRV were greater than for olanzapine, aripiprazole, ziprasidone or risperidone. Attention should be paid to controlling the dosage of clozapine combination and clozapine and monitoring the patient’s electrocardiogram during administration.