OBJECTIVE. To determine the cost effectiveness of several cervical cancer screening strategies utilizing HPV testing in South Africa. METHODS. We developed a lifetime Markov model of the costs, quality of life, and survival associated with screening and treating cervical cancer and its precursors. Screening strategies evaluated included: 1) conventional cytology, 2) cytology followed by HPV testing for triage of equivocal cytology, 3) HPV testing, 4) HPV testing followed by cytology for triage of HPV-positive women, and 5) co-screening with cytology and HPV testing. Primary outcome measures included quality-adjusted life-years saved (QALYs), incremental cost-effectiveness ratios, and lifetime risk of cervical cancer. Costs are in 2006 South African Rand (R). RESULTS. In a cohort of 100,000 women, starting at age 30 and screening once every 10 years reduced the lifetime risk of cervical cancer by 13–52k depending on the screening strategy used, at an incremental cost of R13,000–R42,000 per QALY. When strategies were compared incrementally, cytology with HPV triage was less expensive and more effective than screening using cytology alone. HPV testing with the use of cytology triage was a more effective strategy and costs an additional R42,121 per QALY. HPV testing with colposcopy for HPV-positive women was the next most effective option at an incremental cost of R1541 per QALY. Simultaneous HPV testing and cytology co-screening was the most effective strategy and had an incremental cost of R25,414 per QALY. CONCLUSIONS. In our model, HPV testing to screen for cervical cancer and its precursors is a cost-effective strategy in South Africa.