BACKGROUND: Positive screening results are often associated not only with target-disease-specific but also with non-target-disease-specific mortality. In general, this association is due to joint risk factors. Cost-effectiveness estimates based on decision-analytic models may be biased if this association is not reflected appropriately. OBJECTIVE: To develop a procedure for quantifying the degree of bias when an increase in non-target-disease-specific mortality is not considered. METHODS: We developed a family of parametric functions that generate hazard ratios (HRs) of non-target-disease-specific mortality between subjects screened positive and negative, with the HR of target-disease-specific mortality serving as the input variable. To demonstrate the efficacy of this procedure, we fitted a function within the context of coronary artery disease (CAD) risk screening, based on HRs related to different risk factors extracted from published studies. Estimates were embedded into a decision-analytic model, and the impact of 'modelling increased non-target-disease-specific mortality' was assessed. RESULTS: In 55-year-old German men, based on a risk screening with 5 % positively screened subjects, and a CAD risk ratio of 6 within the first year after screening, incremental quality-adjusted life-years were 19 % higher and incremental costs were 8 % lower if no adjustment was made. The effect varied depending on age, gender, the explanatory power of the screening test and other factors. CONCLUSION: Some bias can occur when an increase in non-target-disease-specific mortality is not considered when modelling the outcomes of screening tests.