Objective: To reduce socioeconomic inequalities in uptake of the NHS BCSP ’ s guaiac faecal occult blood test (gFOBt) without compromising uptake in any socioeconomic group. Design: Workstream 1 explored psychosocial determinants of non-uptake of gFOBt in focus groups and interviews. Workstream 2 developed and tested four theoretically based interventions: (1) ‘ gist ’ information, (2) a ‘ narrative ’ leaflet, (3) ‘ general practice endorsement ’ (GPE) and (4) an ‘ enhanced reminder ’ (ER). Workstream 3 comprised four national cluster randomised controlled trials (RCTs) of the cost-effectiveness of each intervention. Methods: Interventions were co-designed with user panels, user tested using interviews and focus groups, and piloted with postal questionnaires. RCTs compared ‘ usual care ’ (existing NHS BCSP invitations) with usual care plus each intervention. The four trials tested: (1) ‘ gist ’ leaflet ( n = 163,525), (2) ‘ narrative ’ leaflet ( n = 150,417), (3) GPE on the invitation letter ( n = 265,434) and (4) ER ( n = 168,480). Randomisation was based on day of mailing of the screening invitation. The Index of Multiple Deprivation (IMD) score associated with each individual ’ s home address was used as the marker of socioeconomic circumstances (SECs). Change in the socioeconomic gradient in uptake (interaction between treatment group and IMD quintile) was the primary outcome. Screening uptake was defined as the return of a gFOBt kit within 18 weeks of the invitation that led to a ‘ definitive ’ test result of either ‘ normal ’ (i.e. no further investigation required) or ‘ abnormal ’ (i.e. requiring referral for further testing). Difference in overall uptake was the secondary outcome. Results: The gist and narrative trials showed no effect on the SECs gradient or overall uptake (57.6% and 56.7%, respectively, compared with 57.3% and 58.5%, respectively, for usual care; all p -values > 0.05). GPE showed no effect on the gradient ( p = 0.5) but increased overall uptake [58.2% vs. 57.5% in usual care, odds ratio (OR) = 1.07, 95% confidence interval (CI) 1.04 to 1.10; p < 0.0001]. ER showed a significant interaction with SECs ( p = 0.005), with a stronger effect in the most deprived IMD quintile (14.1% vs. 13.3% in usual care, OR = 1.11, 95% CI 1.04 to 1.20; p = 0.003) than the least deprived (34.7% vs. 34.9% in usual care OR = 1.00, 95% CI 0.94 to 1.06; p = 0.98), and higher overall uptake (25.8% vs. 25.1% in usual care, OR = 1.07, 95% CI 1.03 to 1.11; p = 0.001). All interventions were inexpensive to provide. Limitations: In line with NHS policy, the gist and narrative leaflets supplemented rather than replaced existing NHS BCSP information. This may have undermined their effect. Conclusions: Enhanced reminder reduced the gradient and modestly increased overall uptake, whereas GPE increased overall uptake but did not reduce the gradient. Therefore, given their effectiveness and very low cost, the findings suggest that implementation of both by the NHS BCSP would be beneficial. The gist and narrative results hig...