OBJECTIVES: To systematically appraise the literature on the accuracy of four widely used tests to diagnose Pancreatic Exocrine Insufficiency (PEI) secondary to chronic pancreatitis (CP), gastrointestinal/pancreatic surgery or pancreatic cancer in Spain, namely: coefficient of fat absorption (CFA); mixed 13C-triglyceride breath test (MTG); fecal elastase-I (FE-I); and serum nutritional markers (SNM).  METHODS: A systematic review of the literature (March, 2013) was performed (MedLine/PubMed, Cochrane Library, CRD, MEDION, ARIF, MEDES, IBECS, ISI WOK, SCOPUS), based on the Cochrane and NHS Centre for Reviews and Dissemination recommendations for reviewing diagnostic test accuracy studies. Expert validation of the review strategy and results were achieved by two consensus meetings.  RESULTS: Out of 13.379 publications, 16 from the systematic search and 3 from hand-search were reviewed: 11 in CP and 8 in cancer/surgery patients. Fourteen of these used the secretin/cerulein test as the reference standard. According to experts, CFA is the gold standard for PEI diagnosis (assumed accuracy 100%). 4 publications using CFA as the reference standard were selected: FE-I sensitivity and specificity in 58 CP (cutoff <218μg/g) and 40 cancer/surgery patients (cutoff 200μg/g) were 68% and 98%, and 91% and 35%, respectively. MTG was ≥90% sensitive and specific in all populations (63 patients), experts considered this a good reference standard. Sensitivity and specificity for SNM vs. MTG were 80% and 81%, respectively and considered by experts as similarly accurate in the cancer/surgery population.  CONCLUSIONS: This is the first systematic review to confirm the accuracy of four diagnostic tests for PEI in CP and cancer/surgery patients, with the final selection of results being based on expert consensus to ensure that the data are representative of Spanish clinical practice. These data, together with resource use and cost information from clinical practice will feed an economic tool to assess the cost of PEI diagnosis in Spain.