Background: Arterial cannulation is usually indicated for both sampling and invasive pressure monitoring. Radial artery access is increasingly favored over other sites for arterial cannulation. However, radial cannulation in morbidly obese patients is an anesthetic challenge. This study evaluates the effect of subcutaneous infiltration of nitroglycerine on radial artery cannulation in morbidly obese patients. Sixty patients were randomly allocated into two equal groups according to subcutaneous infiltrate used before radial artery cannulation. In the LN group, the syringe contains 0.2 ml of nitroglycerine (NTG) plus 0.8 ml lidocaine hydrochloride 2%, while in L group, the syringe is filled with 1 ml of lignocaine 2%. Results: Subcutaneous infiltration of the lignocaine-NTG mixture in the LN group resulted in a significant increase in arterial dimensions in comparison to lignocaine alone in the L group. Consequently, a significantly higher overall success rate, first attempt success was observed in the LN group. Also, insertion time and number of attempts were significantly lower in the LN group in relation to the L group. Conclusions: Subcutaneous infiltration of nitroglycerin mixed with a lignocaine before ultrasound-guided radial artery cannulation increases the procedure success rate with no detected side effects.