Generation of airborne particulate matter during the handling and opening of various syringe and needle packages in a laminar-airflow workbench (LAFW) and in a biological safety cabinet (BSC) was measured to compare the effects on air cleanliness conditions (International Organization for Standardization [ISO] class 5 within the LAFW or BSC and ISO class 7 in buffer areas). Twenty-five to 50 packages of each of 12 needle or syringe products were opened. Probes were configured to count airborne particles during the separation of strip packages and the opening of packages by peeling back the top web or pushing the device through the packaging (for soft packages) or by twisting apart hard packages. The numbers of particles were not significantly different between the LAFW and BSC. The separation of strip packages generated visible particles and raised airborne particle counts. Peeling open plastic film packages and opening hard plastic packages generated fewer airborne particulates than did pushing devices through the packaging. For all methods of package opening, average counts downstream from the direct compounding area exceeded ISO class 5 conditions. Counts in the LAFW buffer area did not exceed ISO class 7. All methods of separating and opening the packaging of needles and syringes generated particles. The peel-and-present technique generated the lowest particulate volume. The LAFW and BSC were equally effective in maintaining low particle counts.