World Health Organization guidelines recommend that cervical cancer screening programs should prioritize screening coverage in women aged 30 to 49 years. Decisions about target ages and screening frequency depend upon local burden of disease, costs, and capacity. We used cost and test performance data from the START-UP demonstration projects in India, Nicaragua, and Uganda to evaluate the cost-effectiveness of screening at various start ages, intervals, and frequencies. We calibrated a mathematical simulation model of cervical carcinogenesis to each country and compared screening with careHPV (cervical and vaginal sampling), visual inspection with acetic acid (VIA), and cytology between the ages of 25 and 50 years, at frequencies of once to three times in a lifetime, at 5- and 10-year intervals. Screening with careHPV (cervical sampling) was the most effective and cost-effective strategy in all settings; careHPV (vaginal sampling) was only slightly less effective. The most critical ages for screening are between ages 30 and 45 years. Within this age range, screening at certain ages may be relatively more cost-effective, but cancer risk reductions are similar for a given screening test and interval. Screening three times between 30 and 45 years was very cost-effective and reduced cancer risk by ~50%.