Author summary Functional enrichment analysis is a commonly used technique to identify trends in large scale biological datasets. In biomedicine, functional enrichment analysis of gene expression data is frequently applied to identify disease and drug mechanisms. While enrichment tests were once primarily conducted with complicated computer scripts, web-based tools are becoming more widely used. Users can paste a list of genes into a website and receive enrichment results in a matter of seconds. Despite the popularity of these tools, there are concerns that statistical problems and incomplete reporting are compromising research quality. In this article, we conducted a systematic examination of published enrichment analyses and assessed whether (i) any statistical flaws were present and (ii) sufficient methodological detail is provided such that the study could be replicated. We found that lack of methodological detail and errors in statistical analysis were widespread, which undermines the reliability and reproducibility of these research articles. A set of best practices is urgently needed to raise the quality of published work.