Background: Video capsule endoscopy provides noninvasive visualization of the small bowel, but yield is often limited by debris. At our institution, preparation with polyethylene glycol (PEG) and simethicone is used to improve visualization. Aims: We hypothesized that linaclotide and simethicone would yield equal to better results. Methods: We enrolled 29 subjects for the experimental regimen of linaclotide and simethicone. We maintained standard NPO status, clear liquid period, and simethicone dose. Subjects received 290 μg of linaclotide 1 h prior to capsule. We randomly selected 30 historical PEG controls. Two blinded gastroenterologists graded visualization as ideal/excellent, good, fair, or poor and measured small bowel transit time. Results: Thirteen men and 16 women were enrolled with an average age of 61. There was no significant difference in exam quality between linaclotide and control. Preparation was rated as ideal/excellent or good in 19 of 28 of linaclotide and 18 of 28 PEG subjects when recorder entered the small bowel (p = 0.78, chi-square). Median small bowel transit was 192 min (linaclotide) versus 202 min (PEG), respectively (p = 0.93, t test). Three studies (1 linaclotide and 2 PEG) failed to leave the stomach; 1 linaclotide subject had recorder failure. Diagnostic yield was similar (18/29 for linaclotide and 16/30 for PEG, p = 0.50, chi-square). There were no serious side effects. No differences in age, sex, BMI, or frequency of diabetes, GERD, or gastroparesis were measured between the groups. Conclusions: Single-dose linaclotide 1 h before capsule endoscopy was equally effective when compared to PEG in terms of visualization and transit time. This trial was registered at ClincialTrials.gov, number NCT02465385.