Background: It is generally perceived that sample sizes of randomized clinical trials (RCTs) have increased over the years, particularly in specialties such as cardiology, with a robust evidence base. The aim of this study was to analyze temporal trends in sample sizes of RCTs in cardiology journals compared to other specialties. Methods: Abstracts of RCTs involving humans from PubMed for 1970-2013 were analyzed using a digital search algorithm. Sample sizes of studies were extracted from each abstract. Date of publication and journal name were collected. Journals from several medical subspecialties were selected for comparison, using the journal impact factor as a measure of clinical relevance. Sample sizes of studies in 1990 were compared to 2010 for each of the journals using the Mann-Whitney U test. Graphical comparisons of sample size trends are presented. Results: 272,054 abstracts of human RCTs were identified. Median sample sizes for the years 1990 and 2010 is shown in table 1. The median sample size for all RCTs published in Circulation was 99 subjects per study in 1990, increasing to 630 subjects per study in 2010 (p < 0.01). All cardiology journals had a significant increase in study sample size over the 20 year period, as did the multispecialty journals (JAMA, NEJM, Lancet). In contrast, only a few non-cardiology specialty journals published studies with increasing sample sizes (table 1). Figure 1 shows the sample size trend for 1970-2013. Conclusions: Our study demonstrates a dramatic temporal trend of increasing sample sizes in RCTs in cardiology compared to other specialties. Since sample size is estimated based on the effect size studied, one explanation for this observation is that the more obvious larger effects have been previously elucidated, leaving only smaller associations to be studied. This requires increasing resources, highlighting the importance of alternate study designs and collaborative registries to develop a cost effective evidence base.