To evaluate whether the introduction of the 2015 Guidelines for Cardiopulmonary Resuscitation were associated with a change in outcomes after out-of-hospital cardiac arrest (OHCA). Patients with OHCA were divided into adults (≥18 years) and paediatric cases (<18 years). An interrupted time-series analysis was used to compare survival before (pre-guidelines 1 January 2013 to 31 October 2015) and after (post-guidelines 1 May 2016 to 31 December 2018) introduction of the 2015 guidelines. We fitted a regression model after dividing the time-period into segments with separate intercept and slope estimates. We included 309 499 adults and 8668 children with OHCA. There was no difference in the change in survival to hospital discharge with a favourable functional outcome per year between the two periods for adults {slope difference: -0.07% [95% confidence interval (CI) -0.30 to 0.16], P = 0.55} and paediatric cases [slope difference: -0.01% (95% CI -1.35 to 1.32), P = 0.98]. Likewise, we found no immediate change in survival to hospital discharge with a favourable functional outcome between the two periods for adults [0.20% (95% CI -0.21 to 0.61), P = 0.33] and paediatric cases [-1.08 (95% CI -3.44 to 1.27), P = 0.37]. Publication of the 2015 Guidelines for Cardiopulmonary Resuscitation was not associated with an increase in survival to hospital discharge with a favourable functional outcome after OHCA. Outcomes for OHCA have not improved the last 6 years in the USA.