OBJECTIVE: To investigate and compare seven types of injection devices for their risks of iatrogenic transmission of bloodborne pathogens and their economic costs in sub-Saharan Africa. METHODS: Risk assumptions for each device and cost models were constructed to estimate the number of new hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections resulting from patient-to-patient, patient-to-health care worker, and patient-to-community transmission. Costs of device purchase and usage were derived from the literature, while costs of direct medical care and lost productivity from HBV and HIV disease were based on data collected in 1999 in Côte d'Ivoire, Ghana, and Uganda. Multivariate sensitivity analyses using Monte Carlo simulation characterized uncertainties in model parameters. Costs were summed from both the societal and health care system payer's perspectives. FINDINGS: Resterilizable and disposable needles and syringes had the highest overall costs for device purchase, usage, and iatrogenic disease: median US dollars 26.77 and US dollars 25.29, respectively, per injection from the societal perspective. Disposable-cartridge jet injectors and automatic needle-shielding syringes had the lowest costs, US dollars 0.36 and US dollars 0.80, respectively. Reusable-nozzle jet injectors and auto-disable needle and syringes were intermediate, at US dollars 0.80 and US dollars 0.91, respectively, per injection. CONCLUSION: Despite their nominal purchase and usage costs, conventional needles and syringes carry a hidden but huge burden of iatrogenic disease. Alternative injection devices for the millions of injections administered annually in sub-Saharan Africa would be of value and should be considered by policy-makers in procurement decisions.