The science community generally believes that the violation of research integrity is rare. Built upon this belief, the scientific system makes little effort to examine the trustworthiness of research. Research misconduct refers to an intentional violation of research integrity principles, which has an extensive and far-reaching impact on the trustworthiness and reputation of science. Emerging evidence has suggested that research misconduct is far more common than we normally perceive. Far more problematic papers should be retracted than are being retracted because of poor actions when confronting research misconduct. Research misconduct is usually driven by incentives in the form of pursuing publications for researchers’ career needs and is further facilitated by poor research governance. The current strategy that tackles potential research misconduct focuses on protecting the reputation of authors and their institutions but neglects the interests of patients, clinicians and honest researchers. Removing improper incentives, training researchers and imposing better governance are vital to reducing research misconduct. Awareness of the possibility of misconduct and formalized procedures that scrutinize study trustworthiness are important during peer review and in systematic reviews.