Evidence has the potential to be misleading if its value when expressing beliefs in hypotheses is not fully understood or presented. Although the knowledge base to understand uncertainties is growing, a challenge remains to prioritise research and to continuously assess the magnitude and consequences of misleading evidence in criminal cases. This study used a systematic content analysis to identify misleading evidence, drawing information from case transcripts of rulings argued unsafe by the Court of Appeal of England and Wales. In the 7-year study period, 218 applications were successful on appeal, containing 235 cases of misleading evidence. The majority (76%) of successful appeals were based upon the same materials available in the original trial, rather than the presentation of new relevant information. Witness (39%), forensic (32%), and character evidence (19%) were the most commonly observed evidence types, with the validity of witnesses (26%), probative value of forensic evidence (12%), and relevance of character evidence (10%) being the most prevalent combinations of identified issues. Additionally, the majority (66%) of misleading evidence types relate to their interpretation at activity level. The findings suggest that many of these misleading aspects could have been prevented by providing more transparency in the relationship between evidence and hypotheses. Generally, the results contribute to gaining a more complete picture of the role of misleading evidence in the criminal justice system.