This study examined the effects of a simultaneous ischemic preconditioning (IPC) and SHAM intervention to reduce the placebo effect due to a priori expectation on the performance of knee extension resistance exercise. Nine moderately trained men were tested in three different occasions. Following the baseline tests, subjects performed a first set of leg extension tests after the IPC (3 X 5 min 50 mmHg above systolic blood pressure) on right thigh and the SHAM (same as IPC, but 20 mmHg) on left thigh. After 48 hours, the subjects performed another set of tests with the opposite applications. Number of repetitions, maximal voluntary isometric contraction (MVIC) and perceptual indicators were analyzed. After IPC and SHAM intervention performed at the same time, similar results were observed for the number of repetitions, with no significant differences between conditions (baseline x IPC x SHAM) for either left (p = 0.274) or right thigh (p = 0.242). The fatigue index and volume load did not show significant effect size after IPC and SHAM maneuvers. In contrast, significant reduction on left tight MVIC was observed (p = 0.001) in SHAM and IPC compared to baseline, but not for right thigh (p = 0.106). Results from the current study may indicate that applying IPC prior to a set of leg extension does not result in ergogenic effects. The placebo effect seems to be related to this technique and its dissociation seems unlikely, therefore including a SHAM or placebo group in IPC studies is strongly recommended.