Background There have been no studies showing that participation in programmes which provide legal access to drug-injection equipment leads to individual-level protection against incident HIV infection. We have compared HIV incidence among injecting drug users participating in syringe-exchange programmes in New York City with that among non-participants. Methods We used meta-analytic techniques to combine HIV incidence data from injecting drug users in three studies: the Syringe Exchange Evaluation (n=280), in which multiple interviews and saliva samples were collected from participants at exchange sites; the Vaccine Preparedness Initiative cohort (n=133 continuing exchangers and 188 non-exchangers, in which participants were interviewed and tested for HIV every 3 months; and very-high-seroprevalence cities in the National AIDS Demonstration Research (NADR) programme (n=1029), in which street-recruited individuals were interviewed and tested for HIV every 6 months. In practice, participants in the NADR study had not used syringe exchanges. Findings HIV incidence among continuing exchange-users in the Syringe Exchange Evaluation was 1 . 58 per 100 person . years at risk (95% CI 0 . 54, 4 . 65) and among continuing exchange-users in the Vaccine Preparedness Initiative it was 1 . 38 per 100 person-years at risk (0 . 23, 4 . 57), Incidence among non-users of the exchange in the Vaccine Preparedness Initiative was 5 . 26 per 100 person-years at risk (2 . 41, 11 . 49), and in the NADR cities, 6 . 23 per 100 person-years at risk (4 . 4, 8 . 6). In a pooled-data, multivariate proportional-hazards analysis, not using the exchanges was associated with a hazard ratio of 3 . 35 (95% CI 1 . 29, 8 . 65) for incident HIV infection compared with using the exchanges. Interpretation We observed an individual-level protective effect against HIV infection associated with participation in a syringe-exchange programme. Sterile injection equipment should be legally provided to reduce the risk of HIV infection in persons who inject illicit drugs.