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Postoperative paralytic ileus prolongs hospitalization duration, increases medical expenses, and is even associated with postoperative mortality; however, effective prevention of postoperative paralytic ileus is not yet available. This trial aimed to assess the preventative effectiveness of transcutaneous electrical acupoint stimulation applied in the lower limbs on postoperative paralytic ileus incidence after colorectal surgery. After ethics approval and written informed consent, 610 patients from 10 hospitals who were scheduled for colorectal surgery between May 2018 and September 2019 were enrolled. Patients were randomly allocated into the transcutaneous electrical acupoint stimulation (stimulated on bilateral Zusanli, Shangjuxu, and Sanyinjiao acupoints in lower limbs for 30 minutes each time, total 4 times) or sham (without currents delivered) group with 1:1 ratio. The primary outcome was postoperative paralytic ileus incidence, defined as no flatus for >72 hours after surgery. Compared to the sham treatment, transcutaneous electrical acupoint stimulation lowered the postoperative paralytic ileus incidence by 8.7% (32.3% vs 41.0%, P =.026) and decreased the risk of postoperative paralytic ileus by 32% (OR, 0.68; P =.029). Transcutaneous electrical acupoint stimulation also shortened the recovery time to flatus, defecation, normal diet, and bowel sounds. Transcutaneous electrical acupoint stimulation treatment significantly increased median serum acetylcholine by 55% (P =.007) and interleukin-10 by 88% (P <.001), but decreased interleukin-6 by 47% (P <.001) and inducible nitric oxide synthase by 42% (P =.002) at 72 hours postoperatively. Transcutaneous electrical acupoint stimulation attenuated the postoperative paralytic ileus incidence and enhanced gastrointestinal functional recovery, which may be associated with increasing parasympathetic nerve tone and its anti-inflammatory actions. [ABSTRACT FROM AUTHOR]