Background and study aims For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. Patients and methods Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. Results We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS >= 6) was significantly higher in the simethicone group than in the conventional group (88.2% vs. 76.6%; P < 0.001). The mean (SD) BBPS score was significantly lower in the conventional group (6.5 [1.8] vs. 7.3 [1.7]; P < 0.001), as was the bubble score (2.5 [0.7] vs. 2.8 [0.5]; P < 0.001). The average cecal intubation time was significantly shorter in the simethicone group (6.3 [3.1] vs. 7.5 [5.1] minutes; P < 0.001). The ADR in the right colon was higher in the simethicone group than in the conventional group (16.6% vs. 10.3%; P = 0.03). Safety and compliance, including the taste, smell, and dosage of PEG, were similar for both groups. Conclusions Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR.