Purpose: Ischemic preconditioning (IPC) through purposeful circulatory occlusion may enhance exercise performance. The value of IPC for improving performance is controversial owing to challenges with employing effective placebo controls. This study examines the efficacy of IPC versus a deceptive sham protocol for improving performance to determine whether benefits of IPC are attributable to true physiological effects. It was hypothesized that IPC would favorably alter performance more than a sham treatment and that physiological responses to exercise would be affected only after IPC treatment. Methods: In a randomized order, 16 participants performed incremental exercise to exhaustion on a cycle ergometer in control conditions and after sham and IPC treatments. Participants rated their belief as to the efficacy of each treatment compared with control. Results: Time to exhaustion was greatest after IPC (control = 1331  s, IPC = 1429  s, sham = 1343  s, P = .02), despite negative performance expectations after IPC and positive expectation after sham. Maximal aerobic power remained unchanged after both SHAM and IPC (control = 42.0 [5.2], IPC = 41.7 [5.5], sham = 41.6 [5.5] mL·kg−1·min−1, P = .7), as did submaximal lactate concentration (control = 8.9 [2.6], sham = 8.0 [1.9], IPC = 7.7 [2.1] mmol, P = .1) and oxygen uptake (control = 37.8 [4.8], sham = 37.5 [5.3], IPC = 37.5 [5.5] mL·kg−1·min−1, P = .6). Conclusions: IPC before cycling exercise provides an ergogenic benefit that is not attributable to a placebo effect from positive expectation and that was not explained by traditionally suggested mechanisms.