OBJECTIVES: To systematically evaluate the impact of screening adherence on clinical effectiveness and cost-effectiveness of cervical cancer screening (CCS) in Germany using a decision analytic approach. METHODS: A decision-analytic Markov model was used to evaluate long-term clinical and economic outcomes for the following CCS strategies: 1) no screening, 2) conventional Papanicolaou test with manual smear analysis (PAP), 3) PAP with automated smear analysis (AA), 4) liquid-based preparation (LP) with manual smear analysis and 5) LP in combination with AA. German clinical, epidemiological and economic data were used. German clinical practice in screening, diagnosis, and treatment of cervical cancer and its precursors were considered. Calculated outcomes were detected/prevented cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER). We adopted a societal perspective with a three percent (3%) annual discount rate. In the absence of individual data, screening adherence was modeled to be independent from screening history. RESULTS: In women adherent to screening, annual PAP saved 94 life days, when compared to “no screening”, and new CCS strategies saved additional 0.5 days. Assuming 50% adherence annual screening with new strategies would save additional 3 days compared to annual PAP screening with 50% adherence and would be nearly equally effective as annual PAP with complete adherence. Assuming a societal willingness-to-pay of 50,000€/LYS, annual PAP compared to “no screening” was cost-effective independent of screening adherence. Annual screening with new strategies compared to PAP was not cost-effective in adherent women, but may be cost-effective with 65% (AA) or 40% (LP or LP+AA) or lower adherence. CONCLUSIONS: For the current clinical standard of annual cervical cancer screening in Germany, PAP screening is both medical effective and cost-effective independent of adherence. New CCS strategies may be effective and cost-effective in women who do not regularly attend annual screening programs.