Introduction: Process research in psychotherapy is important to understand how treatment works. The National Institute of Clinical Excellence guidelines suggest that in methadone maintenance treatment (MMT) for opioid dependence, drug key-working should be based on cognitive behavioural therapy (CBT) principles. This article reports the findings of process research component of a larger study investigating the effectiveness and cost-effectiveness of CBT in MMT in the UK (UKCBTMM project). Method: This was a multicentre randomized controlled trial comparing MMT plus CBT with MMT alone. The following concepts have been measured as part of the process research: (i) coping skills, (ii) self-efficacy and (iii) outcome expectancies. Results: CBT group has gained coping skills over time (as predicted) at 6 months, which were sustained at 12 months. Self-efficacy showed delayed greater increase in the CBT group at 12 months (as predicted). Positive outcome expectancies from reduction of drug use were reduced for the CBT group both at 6 and 12 months whereas negative expectancies had increased (against prediction). Conclusions: As this is the first trial in which the process changes in CBT in opioid dependence have been explored, the reported limited findings are of importance for further development in the field. (Contains 1 table.)