Abstract: Human patient simulation manikins (HPSMs) are being used extensively in the education of health professionals, but their effectiveness in the teaching of clinical reasoning skills to undergraduate nursing students is not clear. The aim of this systematic review is to identify the best available evidence for their effectiveness in this regard. The review included all English-language randomized controlled trials from 1999 to 2009 that assessed the effectiveness of high-fidelity HPSMs in educating undergraduate nursing students. The results indicate that the use of HPSMs improves knowledge acquisition and critical thinking and enhances students’ satisfaction with the learning. There is a lack of unequivocal evidence of the effectiveness of using high-fidelityHPSMsin the teaching of clinical reasoning skills to undergraduate nursing students. Further research is required to ascertain the effectiveness of the use of HPSMs as an educational strategy to improve the clinical reasoning skills of undergraduate nursing students.