OBJECTIVES: The objective of this health technology assessment commissioned by the German Agency for Health Technology Assessment at DIMDI/German Federal Ministry of Health was to conduct a systematic review of the cost-effectiveness of new cervical cancer screening techniques, and to perform a decision-analysis in the context of the German health care system. METHODS: A systematic literature review and assessment on quality/transferability of data was performed using instruments developed by the German Scientific Working Group Technology Assessment for Health Care. The German Cervical Cancer Model Group, an international and interdisciplinary network, was established to (1) assess German clinical practice patterns; (2) create a database of German epidemiological, clinical, and economic model parameters; (3) develop a German decision model based on previously published and validated international models, and (4) perform cost-effectiveness analyses. RESULTS: Based on international studies, the discounted incremental cost-effectiveness ratios (ICER) compared to conventional smears were US$10,000-37,000 per life year saved (LYS) for liquid based testing, 22,000-29,000 US$/LYS for automated primary screening, and 16,000-48,000 US$/LYS for automated re-screening technologies, assuming a 3-year screening interval, but was much less attractive for more frequent screening intervals. In comparison, for the German health care context screening with a combination of liquid-based preparation plus computer-assisted smear-analyses compared to conventional smears resulted in 31,000 €/LYS for a 3-year screening interval, 56,000 €/LYS for a 2 year screening interval, and 300,000 €/LYS for annual screening. Results were most sensitive to assumptions about the costs and performance of screening tests and population compliance. CONCLUSIONS: Technologies improving performance of cervical cancer screening are reasonably cost-effective at screening intervals of three years and greater. Based on the current clinical standard of annual cervical cancer screening in Germany, the introduction of new screening technologies would likely not be cost-effective without a reduction in screening frequency.