Objective: The objective of this study was to examine effectiveness of co-designed quality-improving interventions with a multidisciplinary team (MDT) with high workload and prolonged meetings to ascertain: (1) presence and impact of decision-making (DM) fatigue on team performance in the weekly MDT meeting, and (2) impact of a short meeting break as a countermeasure of DM fatigue.Design and interventions: This is a longitudinal multiphase study with a co-designed intervention bundle assessed within team audit and feedback cycles. The interventions comprised short meeting breaks, as well as change of room layout and appointing a meeting chair.Setting and participants: A breast cancer MDT with 15 members was recruited between 2013 and 2015 from a teaching hospital of the London (UK) metropolitan area. Measures: A validated observational tool (Metric for the Observation of Decision-making, MDT-MODe) was used by trained raters to assess quality of DM during 1,335 patient-reviews. The tool scores quality of information and team contributions to reviews by individual disciplines (Likert-based scores), which represent our two primary outcome measures. Results: Data were analysed using multivariate analysis of variance. DM fatigue was present in the MDT meetings: quality of information (M=16.36 to M=15.10) and contribution scores (M=27.67 to M=21.52) declined from 1st to 2nd half of meetings at baseline. Of the improvement bundle, we found breaks reduced the effect of fatigue: following introduction of breaks (but not other interventions) information quality remained stable between 1st and 2nd half of meetings (M=16.00 to M=15.94), and contributions to team DM improved overall (M=17.66 to M=19.85). Conclusion: Quality of cancer team DM is affected by fatigue due to sequential case-review over often prolonged periods of time. This detrimental effect can be reversed by introducing a break in the middle of the meeting. The study offers a methodology based on ‘team audit and feedback’ principle for co-designing interventions to improve teamwork in cancer care.