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Key Points Question Does the language of medicine in academic journals indicate whether the culture of clinical investigation has shifted toward patient centeredness? Findings In this qualitative study of medical language of 302 293 articles from 5 premier medical journals, use in the last 40 years has changed to reflect a shift from individuals to populations, a separation of patient and disease, and an increase in patient-centric titles. Meaning Whereas medical language previously emphasized treatments and disease processes, the trend during the last 40 years has been to separate patients from their disease and to emphasize the patient rather than characterize patients by their disease., This qualitative study of medical research language assesses changes in 5 medical journals and broader changes in the culture of clinical investigation during the last 40 years., Importance The language of medical research appears to be intrinsically tied to the culture of medical research and provides a unique window into broader trends in the culture of medicine. Objective To analyze medical language from 5 premier medical journals and investigate broader changes in the culture of clinical investigation during the last 40 years. Design, Setting, and Participants In this qualitative study using a data-driven analysis, 302 293 PubMed records were extracted from JAMA, The Lancet, Annals of Internal Medicine, the BMJ, and New England Journal of Medicine from January 1, 1976, through December 31, 2015, to identify key trends in medical language. A frequency analysis was applied across the 40-year time frame in JAMA to assess the major trends in all publication types. Patient-centered language was analyzed in clinical trials in the flanking time periods (1976-1980 and 2011-2015) across the 5 journals. Data were analyzed from November 16, 2016, through November 9, 2018. Main Outcomes and Measures Increasing or decreasing frequency of words (monograms) and word pairs (bigrams) and the proportion of patient-centric words in journal article titles. Results In JAMA, 50 277 articles of all publication types were included. In the frequency analysis, the most increased terms were reflective of the language of epidemiological research. The bigram analysis revealed a decline in causal language (−2.42/100 000 words to −2.03/100 000 words; false discovery rate [FDR]