Background and study aims Men have more colon cleansing failures, colorectal adenomas, and colorectal cancers than women. We analyzed whether 1-liter (1 L) polyethylene glycol (PEG) NER1006 improves high-quality (HQ) colon cleansing and adenoma detection in males versus two mid-volume alternatives. Patients and methods The analysis of 1028 adult patients in two randomized clinical trials was performed. Adenoma detection and HQ cleansing were compared for overnight split dosing regimens with NER1006 (n = 513) versus combined oral sulfate solution or 2 L PEG + ascorbate (OSS/2 L PEG) (n = 515). Analyses included males versus females, overweight or obese (OO) males versus lean males, and NER1006 versus OSS/2 L PEG. In male patients, the adenoma detection rate of at least 3 (ADR3 +) was predicted with multiple logistic regression and statistical comparisons used the two-sided t-test. Results ADR3 + was greater in males versus females (10.7 % [56/524] versus 5.8 % [29/504]; P = 0.004) despite comparable adequate cleansing success rates (93.2 % [479/514] versus 93.0 % [466/501]; P = 0.912) and more HQ-scores in females (41.6 % [1069/2570] versus 45.3 % [1134/2505]; P = 0.008). ADR was almost twice as high in OO versus lean males (43.4 % [184/424] versus 23.1 % [21/91]; P < 0.001). Multivariate logistic regression predicted ADR3 + detection to be twice as likely in OO males using NER1006 versus OSS/2 L PEG (odds ratio (95 % confidence interval [CI]) = 2.049 (1.082–3.973); P = 0.030) and 90 % more likely in all males (1.902 (1.045–3.526); P = 0.037). In males, including OO males, NER1006 attained more HQ-scores per trial than OSS or 2 L PEG (P ≤ 0.017 for all comparisons). Conclusions NER1006 predicted the detection of more males for frequent surveillance than OSS/2 L PEG.