Translating neuroprotective efficacy from animal studies to clinical trials in humans has been fraught with difficulty. This failure might be because animal studies were falsely positive or because clinical trials were falsely negative. Alternatively, animal studies as currently conducted may not model human stroke with sufficient fidelity to be a useful predictor of efficacy in clinical trials. Here we focus on measures to improve the design, conduct, and reporting of animal studies to maximize both their internal and their external validity. These include, but are not limited to, randomization, allocation concealment, blinded assessment of outcome, sample size calculation, and measures to avoid publication bias. In addition, we give a brief introduction to systematic review and meta-analysis of data from animal experiments.