Objective To determine whether two specific criteria in Uniform Requirements for Manuscripts (URM) created by the International Committee of Medical Journal Editors (ICMJE)-namely, including the trial ID registration within manuscripts and timely registration of trials, are being followed. Materials and methods Observational study using computerized analysis of publicly available Medline article data and clinical trial registry data. We analyzed a purposive set of five ICMJE founding journals looking at all trial articles published in those journals during 2010- 2011, and data from the ClinicalTrials.gov (CTG) trial registry. We measured adherence to trial ID inclusion policy as the percentage of trial journal articles that contained a valid trial ID within the article ( journalbased sample). Adherence to timely registration was measured as the percentage of trials that registered the trial before enrolling the first participant within a 60-day grace period. We also examined timely registration rates by year of all phase II and higher interventional trials in CTG (registry-based sample). Results To determine trial ID inclusion, we analyzed 698 clinical trial articles in five journals. A total of 95.8% (661/690) of trial journal articles included the trial ID. In 88.3% the trial-article link is stored within a structured Medline field. To evaluate timely registration, we analyzed trials referenced by 451 articles from the selected five journals. A total of 60% (272/451) of articles were registered in a timely manner with an improving trend for trials initiated in later years (eg, 89% of trials that began in 2008 were registered in a timely manner). In the registry-based sample, the timely registration rates ranged from 56% for trials registered in 2006 to 72% for trials registered in 2011. Discussion Adherence to URM requirements for registration and trial ID inclusion increases the utility of PubMed and links it in an important way to clinical trial repositories. This new integrated knowledge source can facilitate research prioritization, clinical guidelines creation, and precision medicine. Conclusions The five selected journals adhere well to the policy of mandatory trial registration and also outperform the registry in adherence to timely registration. ICMJE's URM policy represents a unique international mandate that may be providing a powerful incentive for sponsors and investigators to document clinical trials and trial result publications and thus fulfill important obligations to trial participants and society.