Abstract Background Five large insecticide-treated net (ITN) programmes and two indoor residual spraying (IRS) programmes were compared using a standardized costing methodology. Methods Costs were measured locally or derived from existing studies and focused on the provider perspective, but included the direct costs of net purchases by users, and are reported in 2005 USD. Effectiveness was estimated by combining programme outputs with standard impact indicators. Findings Conventional ITNs: The cost per treated net-year of protection ranged from USD 1.21 in Eritrea to USD 6.05 in Senegal. The cost per child death averted ranged from USD 438 to USD 2,199 when targeting to children was successful. Long-lasting insecticidal nets (LLIN) of five years duration: The cost per treated-net year of protection ranged from USD 1.38 in Eritrea to USD 1.90 in Togo. The cost per child death averted ranged from USD 502 to USD 692. IRS: The costs per person-year of protection for all ages were USD 3.27 in KwaZulu Natal and USD 3.90 in Mozambique. If only children under five years of age were included in the denominator the cost per person-year of protection was higher: USD 23.96 and USD 21.63. As a result, the cost per child death averted was higher than for ITNs: USD 3,933–4,357. Conclusion Both ITNs and IRS are highly cost-effective vector control strategies. Integrated ITN free distribution campaigns appeared to be the most efficient way to rapidly increase ITN coverage. Other approaches were as or more cost-effective, and appeared better suited to "keep-up" coverage levels. ITNs are more cost-effective than IRS for highly endemic settings, especially if high ITN coverage can be achieved with some demographic targeting.