BACKGROUND: The ongoing TANGO2 (Telephone Assisted CPR. AN evaluation of efficacy amonGst cOmpression only and standard CPR) trial is designed to evaluate whether compression-only cardiopulmonary resuscitation (CPR) by trained laypersons is noninferior to standard CPR in adult out-of-hospital cardiac arrest. This pilot study assesses feasibility, safety, and intermediate clinical outcomes as part of the larger TANGO2 survival trial. METHODS: Emergency medical dispatch calls of suspected out-of-hospital cardiac arrest were screened for inclusion at 18 dispatch centers in Sweden between January 1, 2017, and March 12, 2020. Inclusion criteria were witnessed event, bystander on the scene with previous CPR training, age above 18 years of age, and no signs of trauma, pregnancy, or intoxication. Cases were randomized 1:1 at the dispatch center to either instructions to perform compression-only CPR (intervention) or instructions to perform standard CPR (control). Feasibility included evaluation of inclusion, randomization, and adherence to protocol. Safety measures were time to emergency medical service dispatch CPR instructions, and to start of CPR, intermediate clinical outcome was defined as 1-day survival. RESULTS: Of 11 838 calls of suspected out-of-hospital cardiac arrest screened for inclusion, 2168 were randomized and 1250 (57.7%) were out-of-hospital cardiac arrests treated by the emergency medical service. Of these, 640 were assigned to intervention and 610 to control. Crossover from intervention to control occurred in 16.3% and from control to intervention in 18.5%. The median time from emergency call to ambulance dispatch was 1 minute and 36 s (interquartile range, 1.1-2.2) in the intervention group and 1 minute and 30 s (interquartile range, 1.1-2.2) in the control group. Survival to 1 day was 28.6% versus 28.4% (P=0.984) for intervention and control, respectively. CONCLUSIONS: In this national randomized pilot trial, compression-only CPR versus standard CPR by trained laypersons was feasible. No differences in safety measures or short-term survival were found between the 2 strategies. Efforts to reduce crossover are important and may strengthen the ongoing main trial that will assess differences in long-term survival. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02401633.