OBJECTIVES:  To determine the number of unique patient- and clinician-reported outcome (PRO) tools that have been used in studies published since 2005 for different disease areas and populations. METHODS:  We developed a PRO instrument ontology from those tools cited within the abstracts of over 100,000 studies identified by a systematic search of PubMed on the humanistic and economic burden of disease, which were stored in an online database (www.heoro.com). The ontology items are semantically indexed by general topic, population, disease or body area, symptom or treatment. Abstracts are tagged to each relevant ontology item during an automated process using natural language processing and tokenising approaches, and indexing is then checked by experts. RESULTS: A total of 4,272 instruments were identified from 22,254 relevant abstracts. Of these, most (2,648) were disease-specific, 309 related to non-disease-specific treatments, 246 to non-disease-specific symptoms, 243 were for use in children, 117 for caregivers or family members, 70 for the elderly and 13 for clinicians or researchers. Utility values were assessed by 38 instruments. Of the disease-specific instruments, mental disorders had the largest number of different tools (434), followed by musculoskeletal diseases (344 tools), neurological disorders (292), cancers (243), gastrointestinal diseases (231), respiratory diseases (204) and urogenital disorders (172). Treatment-related instruments generally assessed adverse events (100) or satisfaction or effectiveness (92 tools each). Symptom-related instruments most commonly assessed pain (122 tools), urinary incontinence (62), sleep disorders (61) or fatigue (49). CONCLUSIONS: A vast number of different PRO tools have been developed and used in research published over the past 10 years, with a new instrument reported on average for every 5 PRO study publications. The reasons for the diversity remain unclear, but it makes it difficult to compare the impact of diseases on quality of life, or the efficacy and cost-effectiveness of interventions across studies.