OBJECTIVES: To evaluate the most common reasons provided by peer-reviewed journals to reject manuscripts describing data derived from real-world or health-economic (RW/HE) studies. METHODS: Our company project administration records from the last 10 years were reviewed for manuscripts describing HE studies, RW/observational studies (including retrospective database analyses), and patient or disease registries. Reasons for rejection were collected and stratified into “categories”. If more than one reason was provided by the journal, then all reasons were counted. Our analysis was based on industry-sponsored manuscripts for which a complete submission history was available. RESULTS: Rejection letters were collected for 78 manuscripts. Of these, 12 did not specify a reason for rejection. The remaining records revealed a total of 100 rejection counts. The most common reasons were ‘priority rating not high enough’ (33%), ‘concerns about the methodology’ (18%), and ‘information not sufficiently novel’ (15%). Other reasons for rejection included ‘topic not appropriate for the journal’ (7%), ‘manuscript is biased/conclusions are too strong’ (5%), ‘industry involvement not sufficiently disclosed’ (2%), and referral to a sister journal instead (2%). CONCLUSIONS: These common reasons for rejection could provide authors with some guidance on which factors are particularly important to focus on during the development of a RW/HE manuscript to help improve the chances of acceptance by peer-reviewed journals.