**Abstract** **Background:** While opt-out strategies, which assume passive consent to participate, have shown to be effective alternatives to the standard opt-in to increase cancer screening uptake, there is ethical concern about the lack of informed consent. In this study we tested an alternative opt-in strategie, called enhanced active choice, against a standard opt-out invitation for colorectal cancer screening. **Methods:** The study was conducted as part of the Maltese national colorectal cancer screening programme (CRSP) which offers men and women aged 60 to 64 a free faecal occult blood test (FOBTi). 8434 individuals were randomly assigned to either receive an invitation letter that featured an opt-out strategy that required individuals to inform the screening centre if they do not want to participate in the programme (opt-out condition) or an alternative letter with a modified opt-in strategy that presented individuals an active choice that highlighted the benefits of screening (enhanced opt-in condition). We measured acceptance and participation rate at three months after the invitation. **Results:** Overall, 48.4% accepted the invitation and 42.4% did the screening test, independently of the experimental condition. While we did not find statistically significant differences across the two conditions in terms of acceptance (opt-out 47.3% vs enhanced opt-in 48.9%; p=0.16) and participation (opt-out 41.9% vs enhanced opt-out 42.7%; p=0.55), enhanced opt-out increased male participation intentions by 4.6 percentage points (50.8% vs 46.2%; p<0.01) that translated to significant 3.4 percentage points higher participation rate (42.9% vs 39.5%, p=0.04). **Conclusion:** Enhanced opt-in is an equivalent alternative to opt-out or participation by default in terms of uptake rates, with the benefit of enabling individuals to make a more informed decision.