ObjectiveBuilding on Existing Tools To improvE chronic disease pRevention and screening in primary care Wellness of cancer survIvorS and patiEnts (BETTER WISE) was designed to assess the effectiveness of a cancer and chronic disease prevention and screening (CCDPS) programme. Here, we compare outcomes in participants living with and without financial difficulty.DesignSecondary analysis of a cluster-randomised controlled trial.SettingPatients of 59 physicians from 13 clinics enrolled between September 2018 and August 2019.Participants596 of 1005 trial participants who responded to a financial difficulty screening question at enrolment.Intervention1-hour CCDPS visit versus usual care.Outcome measuresEligibility for a possible 24 CCDPS actions was assessed at baseline and the primary outcome was the percentage of eligible items that were completed at 12-month follow-up. We also compared the change in response to the financial difficulty screening question between baseline and follow-up.Results55 of 265 participants (20.7%) in the control group and 69 of 331 participants (20.8%) in the intervention group reported living with financial difficulty. The primary outcome was 29% (95% CI 26% to 33%) for intervention and 23% (95% CI 21% to 26%) for control participants without financial difficulty (p=0.01). Intervention and control participants with financial difficulty scored 28% (95% CI 24% to 32%) and 32% (95% CI 27% to 38%), respectively (p=0.14). In participants who responded to the financial difficulty question at both time points (n=302), there was a net decrease in the percentage of participants who reported financial difficulty between baseline (21%) and follow-up (12%, p<0.001) which was similar in the control and intervention groups. The response rate to this question was only 51% at follow-up.ConclusionThe BETTER intervention improved uptake of CCDPS manoeuvres in participants without financial difficulty, but not in those living with financial difficulty. Improving CCDPS for people living with financial difficulty may require a different clinical approach or that social determinants be addressed concurrently with clinical and lifestyle needs or both.Trial registration numberISRCTN21333761.