Clinical research should ultimately improve patient care. For this to be possible, trials must evaluate outcomes that genuinely reflect real-world settings and concerns. However, many trials continue to measure and report outcomes that fall short of this clear requirement. We highlight problems with trial outcomes that make evidence difficult or impossible to interpret and that undermine the translation of research into practice and policy. These complex issues include the use of surrogate, composite and subjective endpoints; a failure to take account of patients’ perspectives when designing research outcomes; publication and other outcome reporting biases, including the under-reporting of adverse events; the reporting of relative measures at the expense of more informative absolute outcomes; misleading reporting; multiplicity of outcomes; and a lack of core outcome sets. Trial outcomes can be developed with patients in mind, however, and can be reported completely, transparently and competently. Clinicians, patients, researchers and those who pay for health services are entitled to demand reliable evidence demonstrating whether interventions improve patient-relevant clinical outcomes.