ABSTRACT: The relation between heart rate variability (HRV) as non-invasive biomarkers of autonomic function and cognitive behavior therapy (CBT) as non-pharmacological treatments has rarely been examined in patients with constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study is to evaluate the efficacy of an 8-week CBT intervention on HRV and IBS symptoms, and the correlation of changes in HRV with changes in IBS symptoms among young female nursing students with IBS-C.This study consisted of an exploratory subgroup analysis of 43 participants with IBS-C who had been randomly assigned to receive either 8 weeks of CBT (n = 23) or general medical information (control, n = 20). At baseline and 8, 16, and 24 weeks, participants completed a questionnaire assessing their gastrointestinal (GI) symptoms, anxiety, depression, and stress, and their HRV was measured via electrocardiography.At the 8-week follow-up, the high-frequency (HF) power was significantly higher, and the low-frequency (LF)/HF ratio was lower in the CBT group than in the control group (P < 0.001 for both), and the severity of GI symptoms (P = 0.003), anxiety (P < 0.001), depression (P < 0.001), and stress (P < 0.001) was significantly lower in the CBT group than in the control group. Changes in the HF power were significantly and inversely associated with changes in GI symptoms, anxiety, depression, and stress at 16 and 24 weeks (P < 0.05 for all; range of r from -0.37 to -0.68). Changes in the LF/HF ratio were also significantly and positively associated with changes in GI symptoms, anxiety, depression, and stress at 16 and 24 weeks (P < 0.05 for all; range of r from 0.38 to 0.60).CBT was effective in managing symptoms in young IBS-C patients and the improvement of symptoms was sustained at 24 weeks following the completion of CBT. Furthermore, indirect measurement of autonomic function using HRV may be a useful objective parameter for assessing response to CBT in young IBS-C patients.