In systematic reviews, evidence-based practice and journal clubs critical appraisal tools are used to rate research papers. However, little evidence exists on whether the critical appraisal tool, subject matter knowledge or research design knowledge affect the appraisal of research papers. A match paired randomised trial was conducted in August/September 2010 in the Faculty of Medicine, Health and Molecular Science, James Cook University, Australia. Ten participants in total were randomly assigned to two groups using either an informal appraisal of research (IA group) or the Crowe Critical Appraisal Tool (CCAT group), a general critical appraisal tool. Participant independently appraised five research papers, where each paper had a different research design. The scores allocated to the papers by each group were analysed. The intraclass correlation coefficient for absolute agreement was 0.76 for the informal appraisal group and 0.88 for the Crowe Critical Appraisal Tool group. The G study showed that in the informal appraisal group 24% of variance in scores was attributable to either the rater or paper × rater interactions, whereas this was 12% in the Crowe Critical Appraisal Tool group. Analysis of covariance showed that there were statistically significant results in the informal appraisal group for subject matter knowledge (F(1,18) = 7.03, P < 0.05 1 tailed, partial η2 = 0.28) and rater (F(4,18) = 4.57, P < 0.05 1 tailed, partial η2 = 0.50). Kendall's tau correlation coefficient also showed a significant weak positive relationship (τ = 0.38, P = 0.03) between total score and subject matter knowledge for the informal appraisal group. The Crowe Critical Appraisal Tool was more reliable than an informal appraisal of the research papers. In the informal appraisal group, there were significant effects for rater and subject matter knowledge, whereas the Crowe Critical Appraisal Tool almost eliminated the rater effect, and no subject matter knowledge effect was apparent. There was no research design knowledge effect in either group. The Crowe Critical Appraisal Tool provided much better score reliability and should help readers with different levels and types of knowledge to reach similar conclusions about a research paper.