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To review the (1) reliability, validation, feasibility, and clinical utility and (2) the use of the Premature Infant Pain Profile (PIPP) from 1996 to 2009 to determine the effectiveness of pain management strategies.Data sources included MEDLINE, CINAHL, EMBASE, PsycINFO, and the Web of Science. Published studies evaluating the measurement properties of the PIPP and intervention studies using the PIPP as an outcome measure of acute pain were included. One reviewer screened studies for relevance and inclusion. Four reviewers rated intervention studies for methodological quality and extracted data for the evidence tables.Of the 62 studies included, 14 focused on the measurement properties of the PIPP. Reliability of the PIPP was supported in 5 studies and construct validation was supported in 13 studies. The feasibility of the PIPP was addressed in 4 studies, whereas clinical utility was discussed in 2 studies. Twenty-seven of the 48 studies that were considered to have high methodological quality used the PIPP as the major outcome to evaluate the effectiveness of pain management interventions in infants.The PIPP continues to be a reliable and valid measure of acute pain in infants with numerous positive validation studies. There is substantial support for the use of the PIPP as an effective outcome measure in pain intervention studies in infants. Further research with health professionals is required to better support the feasibility and clinical utility of this measure.