We performed a randomized, placebo-controlled, double-blind study to compare the efficacy of intravenous (I.V.) lidocaine and topical nitroglycerin ointment in preventing pain during propofol injection. Nitroglycerin or placebo ointments were applied to the back of the hand over the skin area overlying the I.V. catheter tip; lidocaine was or was not added to the propofol solution. One hundred twenty-four patients were randomly assigned to receive one of four treatments: placebo and plain propofol, propofol mixed with lidocaine, nitroglycerin ointment and plain propofol, and nitroglycerin ointment and propofol mixed with lidocaine. Hence, there were 31 patients in each treatment group. Patients receiving nitroglycerin ointment and plain propofol had the highest incidence of pain on propofol injection (23 of 31 patients, 74%), and the highest median pain score. Only when lidocaine was added to propofol did it effectively reduce the incidence and severity of pain. Patients aged 50 yr and older had a significantly lower incidence and less severe pain. We conclude that lidocaine and age, but not topical nitroglycerin ointment, are factors associated with a decreased incidence of propofol-induced pain.