Objective To identify potential risk factors of occupational needlestick injuries that were not prevented despite adherence to standard precautions. Patients and method Multicentre case control study. Cases were defined as any workers who reported a needlestick injury despite documented use of standard precautions. Controls were workers of the same hospital who had performed procedures similar to matched cases and who reported a needlestick injury without correct use of standard precautions (control 1) or who did not report a needlestick injury during the previous 6 months (control 2). Results A total of 512 injuries were included (256 cases and 256 controls 1), and 256 controls 2. Analyses based on controls 1 showed an increased risk for physicians (ORa 2.22; 95% CI: 1.07-4.60) and those working in the operating theatre (ORa 2.87; 95% CI: 1.26-6.55). Regarding controls 2, increased risks were found for those younger than 25 years (ORa 2.58; 95% CI: 1.20-5.58), physicians (ORa 5.24; 95% CI: 1.50-18.28), those working in operating theatres (ORa 6.00; 95% CI: 2.07-17.36), emergency services, intensive and life-support units (ORa 3.48; 95% CI: 1.37-8.85) and those exposed to poor lighting (ORa 1.67; 95% CI: 1.02-2.82). Education in occupational risk prevention was found to be a protecting factor when controls 1 were analyzed (ORa 0.61; 95% CI: 0.39-0.97). Conclusions Despite adherence to standard precautions, working as a physician, in operating theatres, emergency and life-support units, being younger than 25 years, and being exposed to poor visibility and training in occupational risk prevention appear to be independent risk factors for occupational needlestick injuries.