Objectives To evaluate the relative cost-effectiveness of introducing the RTS,S malaria vaccine in sub-Saharan Africa compared with further scale-up of existing interventions.

Design A mathematical modelling and cost-effectiveness study.

Setting Sub-Saharan Africa.

Participants People of all ages.

Interventions The analysis considers the introduction and scale-up of the RTS,S malaria vaccine and the scale-up of long-lasting insecticide-treated bed nets (LLINs), indoor residual spraying (IRS) and seasonal malaria chemoprevention (SMC).

Main outcome measure The number of Plasmodium falciparum cases averted in all age groups over a 10-year period.

Results Assuming access to treatment remains constant, increasing coverage of LLINs was consistently the most cost-effective intervention across a range of transmission settings and was found to occur early in the cost-effectiveness scale-up pathway. IRS, RTS,S and SMC entered the cost-effective pathway once LLIN coverage had been maximised. If non-linear production functions are included to capture the cost of reaching very high coverage, the resulting pathways become more complex and result in selection of multiple interventions.

Conclusions RTS,S was consistently implemented later in the cost-effectiveness pathway than the LLINs, IRS and SMC but was still of value as a fourth intervention in many settings to reduce burden to the levels set out in the international goals.