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Background: When shared by people who inject drugs, needles and syringes with different dead space may affect the probability of HIV and hepatitis C virus (HCV) transmission differently., Methods: We measured dead space in 56 needle and syringe combinations obtained from needle and syringe programs across 17 countries in Europe and Asia. We also calculated the amounts of blood and HIV that would remain in different combinations following injection and rinsing., Results: Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in length from 8 to 38 mm. The average dead space was 3 μL in low dead space syringes with permanently attached needles, 13 μL in high dead space syringes with low dead space needles, 45 μL in low dead space syringes with high dead space needles, and 99 μL in high dead space syringes with high dead space needles. Among low dead space designs, calculated volumes of blood and HIV viral burden were lowest for low dead space syringes with permanently attached needles and highest for low dead space syringes with high dead space needles., Conclusion: The dead space in different low dead space needle and syringe combinations varied substantially. To reduce HIV transmission related to syringe sharing, needle and syringe programs need to combine this knowledge with the needs of their clients.