Despite early recognition of the theoretical advantages of simulations that include different population subgroups/ strata and different birth cohorts, many modeling-based economic evaluations of cervical screening have been based on unrealistic single birth cohort simulations. The authors examined the effect of a multiple birth cohort simulation on the incremental cost-effectiveness estimates of cervical screening programs, compared to a conventional single cohort simulation. The choice of hypothetical cohort that starts the simulation had a major impact on the cost-effectiveness estimates: Compared with a single birth cohort simulation, the incremental cost-effectiveness of a shift from biennial to triennial screening was 30% higher when using the multiple cohort simulation. Multiple cohort simulations using the different age structures of 4 countries had little impact on the cost effectiveness ratios (variation <5%). Future modeling-based evaluations of screening policies should better reflect the age range of the population that is targeted by carefully specifying the nature of the starting cohort(s).