Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use—when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, π, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of π and randomized to either treatment or placebo with probabilities π and 1-π, respectively. Analysis of the treatment effect includes statistical controls for π (necessary for causal inference) and typically a π-by-treatment interaction. Random assignment of subjects to π and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug.