OBJECTIVES: The pooling of treatment effects estimated from several trials via meta-analysis or network meta-analysis can be confounded by differences across studies; however, advanced methodologies are available to address many of these issues.  Systematic reviews of interventions typically generate a large volume of data and lead to assimilation of a large amount of knowledge by the reviewers. Identifying key variances between trials can be difficult and important nuances can be missed by a meta-analyst. We have designed a novel checklist that highlights key areas of heterogeneity to be considered when designing and undertaking meta-analysis. METHODS: It is important to identify differences early on; hence we have developed a checklist that can be applied to the results of a systematic review of randomised controlled clinical trials. Components of the checklist fall into four domains where heterogeneity may be present: population, interventions, outcomes, and risk of bias. Sections documenting the feasibility of network meta-analysis and recommendations for analysis design are also included. The checklist has been retrospectively applied to a recent NICE technology appraisal; percutaneous vertebroplasty and percutaneous balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures (TA279). RESULTS:   The checklist identified the following sources of heterogeneity in the nine included studies: inclusion criteria, endpoint definitions, endpoint reporting, presence of cross-over, differences in interventions, risk of bias; and within-trial imbalances in baseline characteristics. The checklist suggests that a quality network meta-analysis of this data should exclude one study with high risk of bias, avoid grouping sham procedures and optimal pain management, and control for baseline pain-score to address imbalance across arms. Meta-regression to control for differences in endpoint definitions or inclusion criteria would likely have been infeasible given the low number of studies. CONCLUSIONS: Applying the checklist improved our ability to identify sources of confounding to be addressed or highlighted as caveats in a meta-analysis.