BACKGROUND To assist educators and researchers in improving the quality of medical research, we surveyed the editors and statistical reviewers of high-impact medical journals to ascertain the most frequent and critical statistical errors in submitted manuscripts. RESULTS The Editors-in-Chief and statistical reviewers of the 38 medical journals with the highest impact factor in the 2007 Science Journal Citation Report and the 2007 Social Science Journal Citation Report were invited to complete an online survey about the statistical and design problems they most frequently found in manuscripts. Content analysis of the responses identified major issues. Editors and statistical reviewers (n = 25) from 20 journals responded. Respondents described problems that we classified into two, broad themes: A. statistical and sampling issues and B. inadequate reporting clarity or completeness. Problems included in the first theme were (1) inappropriate or incomplete analysis, including violations of model assumptions and analysis errors, (2) uninformed use of propensity scores, (3) failing to account for clustering in data analysis, (4) improperly addressing missing data, and (5) power/sample size concerns. Issues subsumed under the second theme were (1) Inadequate description of the methods and analysis and (2) Misstatement of results, including undue emphasis on p-values and incorrect inferences and interpretations. CONCLUSIONS The scientific quality of submitted manuscripts would increase if researchers addressed these common design, analytical, and reporting issues. Improving the application and presentation of quantitative methods in scholarly manuscripts is essential to advancing medical research.