OBJECTIVES: Although a number of guidelines are available for the reporting of clinical trials and interventional studies, there is limited consensus in the structure, content and terminology associated with reporting of prospective non-interventional observational studies.  The objective of this study was to describe best practices in reporting of observational studies based on a review of relevant guidelines for reporting data from clinical studies.   METHODS: A systematic literature review was conducted and six relevant guidelines that could be adapted for reporting of results from prospective non-interventional observational studies were identified.  The guidelines reviewed included the FDA guideline for abbreviated clinical study reports (CSR), the EMEA guideline for CSR, the International Conference on Harmonization (ICH) E3 guideline for CSR, Consolidated Standards of Reporting Trials (CONSORT) guideline for pragmatic trials, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline and the International Society for Pharmacoepidemiology (ISPE) guideline for safety reports.  The structure, content, and terminology used in the reporting template recommended by the various guidelines were analyzed.   RESULTS: There were substantial differences in the structure, content and terminology recommended by the six guidelines.  For example, in contrast to all other guidelines, the CONSORT guidelines mention ‘Objectives’ under ‘Methods’ instead of ‘Introduction’.  Under the Results section, for reporting of unadjusted and adjusted estimates from outcomes data, the STROBE guideline recommends its inclusion within the Main Results section, whereas the CONSORT guideline recommends its inclusion within the Outcomes and Estimation section.  Some guidelines, especially those focusing on interventional studies, were more similar in content.   CONCLUSIONS: Based on the evaluation of similarities and differences in the guidelines, we propose a structure and template for reporting of prospective non-interventional observational studies. Recommendations are also provided for adapting the proposed template based on study objectives and design.