Diclofenac is the most widely prescribed non-steroidal anti-inflammatory drug worldwide. Data collected during the last 10 years reported a dose-duration dependent increasing of cardiovascular risk associated with the use of diclofenac, supporting the evidence of a close association with the degree of COX-2 inhibition achieved in vivo. Nevertheless, the amplitude of cardiovascular risk associated with the administration of diclofenac at low doses and for the short-term duration is still poorly defined. Indeed, data did not show a clear and strong increasing of the risk for daily doses of 75 and of 50 mg. Concerning duration, while the identification of a safe temporal window is less defined, some studies reported an absence or a very low risk when the exposure is shorter than 30 days. Today, new low-dosage diclofenac formulations are available, allowing to reduce the systemic exposure, the degree of COX-2 inhibition and possibly the risk of occurrence of cardiovascular events. This is the reason why those new formulations may represent the ideal drug for the management of pain in the emergency setting.