The vasodilatory effects of nitric oxide (NO) have attracted a lot of attention from many investigators who are interested in treatment for cardiovascular disease or hypertension. Recently, however, NO has drawn the attention of people who are looking for new avenues to improve their health, as well as effective ways to enhance exercise performance. In particular, NO, a potent vasodilator, is known to regulate blood flow to active muscles and improve muscle contractile efficiency during exercise, allowing participants to exercise much longer with less fatigue. Neo40TM contains 420mg of a nitric oxide blend with 75mg of caffeine. Therefore, the purpose of the current study was to investigate the effects of Neo40TM on cycling time trial performance and exercise efficiency in 15 moderately trained cyclists. The protocol was a double-blind, randomized, placebo-controlled, two-period, within-subjects crossover study. The treatments were Neo40TM, and a non-caloric similarly favored placebo (PLA). Fifteen participants were randomly assigned to ingest a Neo40 TM or PLA in lozenge form. Exercise performance was assessed by time to complete a simulated 20.15km time-trial course. Exercise efficiency was also measured by VO2 and lactate accumulation at standardized submaximal steady-state exercise intensities. Time-trial performance was enhanced by 2.1% when participants consumed Neo40TM compared to a PLA without a significant difference in rating of perceived exertion (RPE). Time to complete 6km, 10km, 19.5km and 20.15km of cycling was analyzed by gender. A significant difference was found in female subjects at all time points, but not in male subjects. We did not find significant treatment effects for VO2, respiratory exchange ratio (RER), RPE, heart rate (HR) and lactate concentration during steady state exercise. In conclusion, acute supplementation with Neo40TM improved time-trial performance by an average of 2.1% although there were no treatment effects in regards to factors related to work efficiency. / text