OBJECTIVE: 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. METHODS: The incremental cost-effectiveness of three different polio vaccination alternatives was compared to the current schedule of six doses of OPV: (1) IPV at 2, 4 and 6 months; (2) IPV at 6, 10, 14 weeks and 18 months and (3) cessation of polio vaccination. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated. Assumptions about IPV vaccine prices were based on indications from vaccine manufacturers. Treatment costs of polio and the costs of lost productivity were included. The health impact of OPV cessation was measured in terms of Vaccine Associated Paralytic Paralysis [VAPP] cases and Disability Adjusted Life Years [DALYs] averted. One-way sensitivity analysis was performed on the most uncertain variables. RESULTS: The use of OPV in routine immunization services is projected to result in 2.96 VAPP cases in the 2005 cohort. A switch to IPV will increase the total vaccine budget by at least 20%. The cost-effectiveness of the different IPV alternatives varies between US$ 118,000 and US$ 594,000 per discounted DALY averted. 3 doses of IPV in a 10-dose vial is the most cost-effective option. CONCLUSION: Due to the risk of VAPP, it has been recognized that when global polio eradication has been achieved, all countries must cease the use of OPV if the world is to remain polio-free. However, at the assumed vaccine prices, IPV does not appear to be cost-effective in the South African situation. The alternative of ceasing polio vaccination altogether is more economically acceptable, but the perceived risks of this alternative could be a hindrance for its implementation.