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Objective This study examined whether a 4-week group-based mindfulness intervention would be superior in reducing psychological distress in colorectal cancer (CRC) patients compared to a psychoeducation and cognitive behavioural skills learning support active control group. Methods Patients with CRC were randomized via Computerised Permuted Block Randomisation to mindfulness or active control groups (2-h weekly sessions over 4 weeks). Outcomes were measured pre-intervention, and 8 weeks and 6 months post-baseline. The primary outcome was psychological distress measured by the Hospital Anxiety and Depression Scale. Secondary outcomes were generic quality of life (QoL), disease specific QoL, mindfulness, and intervention credibility and acceptability. Results Sixty-eight participants were randomized to mindfulness ( n =35) or active control group ( n =33). Uptake of potentially eligible patients consenting was low (28.0%) and the dropout rate was 33.8%. Depression scores were reduced in both groups at week 8 ( P =0.020). Control participants had greater improvement in generic mental QoL scores at week 8 than mindfulness ( P =0.023). In disease specific QoL, there was reduction in impotence symptom in the mindfulness group ( P =0.022) and reduction in faecal incontinence in the control group ( P =0.019). The embarrassment symptom had a significantly lower increase in the mindfulness group at week 8 compared to the control group ( P =0.009). Both groups rated the treatments as credible and acceptable. Conclusions Mindfulness was not superior to the active control group in terms of alleviating psychological distress but both treatments were associated with some improvements in depression. There was low uptake of both interventions. (Trial registration number: ACTRN12616001033437) Electronic Supplementary Material Supplementary materials (Appendixes) are available in the online version of this article at 10.1007/s11655-023-3632-1.