The aims of this study were to investigate the effects and possible mechanisms of transcutaneous neuromodulation (TN) in patients with chronic constipation. Twelve patients were recruited. The treatment consisted of 2-week TN and 2-week sham-TN which was performed in a crossover design. Bowel habit diary, Patient Assessment of Constipation Symptom (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QOL), and anorectal motility were evaluated. Electrocardiogram was recorded for the assessment of autonomic function during acute TN therapy. It was found that (1) TN improved the frequency of spontaneous defecation. After 2-week TN therapy, 83% patients had more than 3 times bowel movements per week which was significantly different from sham-TN (P=0.01). (2) TN improved PAC-SYM and PAC-QOL scores (P<0.001, resp.). (3) TN significantly decreased the threshold volume to elicit RAIR (P<0.05), ameliorated rectal sensory threshold (P=0.04), and maximum tolerance (P=0.04). (4) TN, but not sham-TN, increased the vagal activity (P=0.01 versus baseline) and decreased the sympathetic activity (P=0.01, versus baseline). It was concluded that needleless TN at posterior tibial nerve and ST36 using a watch-size stimulator is effective in chronic constipation, and the effect was possibly mediated via the autonomic mechanism.