AIMS: To determine whether the introduction of the Universal Form of Treatment Options (the UFTO), as an alternative approach to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders, reduces harms in patients in whom a decision not to attempt cardiopulmonary resuscitation (CPR) was made, and to understand the mechanism for any observed change. METHODS: A mixed-methods before-and-after study with contemporaneous case controls was conducted in an acute hospital. We examined DNACPR (103 patients with DNACPR orders in 530 admissions) and UFTO (118 decisions not to attempt resuscitation in 560 admissions) practice. The Global Trigger Tool was used to quantify harms. Qualitative interviews and observations were used to understand mechanisms and effects. RESULTS: RATE OF HARMS IN PATIENTS FOR WHOM THERE WAS A DOCUMENTED DECISION NOT TO ATTEMPT CPR WAS REDUCED: Rate difference per 1000 patient-days was 12.9 (95% CI: 2.6-23.2, p-value=0.01). There was a difference in the proportion of harms contributing to patient death in the two periods (23/71 in the DNACPR period to 4/44 in the UFTO period (95% CI 7.8-36.1, p-value=0.006). Significant differences were maintained after adjustment for known confounders. No significant change was seen on contemporaneous case control wards. Interviews with clinicians and observation of ward practice revealed the UFTO helped provide clarity of goals of care and reduced negative associations with resuscitation decisions. CONCLUSIONS: Introducing the UFTO was associated with a significant reduction in harmful events in patients in whom a decision not to attempt CPR had been made. Coupled with supportive qualitative evidence, this indicates the UFTO improved care for this vulnerable group. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN85474986 UK Comprehensive Research Network Portfolio 7932.