Background: Bibliometric analyses are used by researchers and research funding agencies to help determine areas of greatest interest, and consequently which topics and domains warrant increased research attention. Bibliometric analyses have similarly been published in a number of clinical subspecialties concerning areas of specific medical interest; however, a thorough literature search revealed that such a study has been absent in the field of thrombolytics to date. To bridge this gap, we conducted a citation analysis of the 100 most influential articles on thrombolytics. Methods: Scopus was selected as the database of choice. Two independent researchers explored the database to extract relevant articles. The articles were ranked according to the number of citations, and a sequential list of the top 100 original articles was prepared in descending order. A detailed analysis was carried out to identify trends and uncover significant discriminators. A second list containing the top 10 review articles was also separately prepared. Results: The 100 most-cited articles regarding thrombolytics were published between 1973 and 2015, with the most articles (n = 29) published in the 5-year period extending from 1996 to 2000. The total number of citations of these 100 most-cited articles ranged from a low of 389 to a high of 6971, with a median of 612.5 citations. These 100 most-cited articles originated from 26 different countries, with more than half from the USA (n = 54), followed by the next most popular countries of origin Germany (n = 20) and France (n = 15). The New England Journal of Medicine (n = 26) and The Lancet (n = 26) contributed the majority of the articles. Conclusion: Our analysis provides insight into the span of research activity and the nature of inquiry dealing with ‘thrombolytic therapy,’ with the hope that such analysis may help to effectively guide future research. Our analysis also yielded a list of the most highly cited and presumably most impactful guideline articles within this field, for distinct consideration.