BACKGROUND Colonoscopy is used for the detection of neoplastic polyps, although a significant miss rate has been reported. Limited data suggest that the administration of the antispasmodic hyoscine N-butylbromide during colonoscopy improves polyp detection. OBJECTIVE To investigate whether the use of 20 mg hyoscine N-butylbromide intravenously during colonoscopy improves polyp detection or removal. METHODS A prospective, double-blind, placebo-controlled, randomized, clinical trial. METHODS Nonacademic teaching hospital. METHODS This study involved 674 patients who were routinely referred and accepted for either diagnostic or screening colonoscopy. METHODS Intravenous injection of either 1 mL hyoscine N-butylbromide (n = 340) or 0.9% NaCl solution (n = 334) when withdrawal was started. METHODS Polyp detection rate (PDR), adenoma detection rate (ADR), and the advanced lesion detection rate (ALDR), 5% trimmed mean number of polyps, mean withdrawal time. RESULTS The cecal intubation rate was 96%. The PDR, ADR, and ALDR were 56% versus 60%, 30% versus 31%, and 14% versus 14% in the hyoscine N-butylbromide and placebo groups, respectively (all P values > .25). The means of the total number of detected, removed, and harvested polyps per patient were 1.13 versus 1.21, 1.03 versus 1.06, and 0.89 versus 0.89 in the hyoscine N-butylbromide and placebo groups, respectively (all P values > .37). Mean withdrawal time was 561 versus 584 seconds in the hyoscine N-butylbromide and placebo groups, respectively (P = .34). Multivariate analysis demonstrated no effect of hyoscine N-butylbromide on the investigated parameters. CONCLUSIONS Only experienced colonoscopists participated in the study. CONCLUSIONS We found no evidence to support the use of hyoscine N-butylbromide during withdrawal of the colonoscope to improve polyp detection or removal. ( BACKGROUND ISRCTN25405865.).