We have studied the effect of non-steroidal antiinflammatory drugs (NSAIDs) on αIIbβ3 integrin activation and platelet aggregation. NSAIDs such as meloxicam, piroxicam, indomethacin and aspirin, but not aceclofenac or diclofenac interfered with the activation state of αIIbβ3. NSAIDs that inhibited αIIbβ3 activation were also able both to partially inhibit platelet primary aggregation and to accelerate platelet deaggregation. These effects of NSAIDs were not dependent on cyclooxygenase inhibition. The results obtained indicate that some NSAIDs exert a specific action on αIIbβ3 activation, and provide an additional mechanism that accounts for their beneficial effects in diseases in which platelet activation is involved.