Ultrasound has been used to aid cannulation of veins of the neck, chest, antecubital fossa, and femoral vein. This investigation compared the traditional method of peripheral intravenous (IV) cannulation of veins of the hands and forearms with ultrasound-guided IV cannulation of these veins. After obtaining institutional review board approval and written informed consent, 35 adult subjects with a history or suspicion of difficult IV cannulation were prospectively enrolled with 16 subjects randomly assigned to the traditional group and 19 to the ultrasound group. Time taken for successful venous cannulation and number of attempts between the groups were compared using a Mann-Whitney U test. The number of subjects in whom IV cannulation was successful on the first attempt was compared between the groups using the Fisher exact test. No significant differences were noted between groups in demographics, time to successful cannulation, number of attempts, and number of subjects in whom IV cannulation was successful on the first attempt. Ultrasound was as efficacious as the traditional method of IV cannulation in this subset of patients. Future investigations should examine the efficacy of the ultrasound-guided technique of IV cannulation of these veins in patients in whom the traditional method failed.