Buyang Huanwu Decoction (BHD) is a well-known Chinese herbal prescription for ischemic stroke. The objective of this systematic review and meta-analysis is to provide the current evidence for neuroprotective effects of BHD and its possible mechanisms in animal models of focal ischemia. A systematic literature search, through October 2012, was performed using six databases. The outcome measures assessed were infarct size and/or neurological score. Fifty-six studies with 1270 animals that met the inclusion criteria were identified. The median score for methodological quality was 3 with a range of 2 to 6. Compared with vehicle or no treatment controls, BHD gave a 37% improvement in outcome for all doses ranging from 1.0 g/kg to 60 g/kg at each time point that BHD was administered (P < 0.01). Efficacy was higher in mouse models that utilized suture occlusion and temporary ischemia. The neuroprotective effects of BHD are involved in multiple mechanisms and act upon multiple cell types. In conclusion, BHD possesses substantial neuroprotective effects in experimental stroke probably as a result of the multitarget therapy strategy typically utilized in traditional Chinese medicine. Future research should examine the presence of possible experimental bias and an in-depth study of herbal compound preparations.