AIMS: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. METHODS: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. CONCLUSIONS: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39.