Cardiopulmonary resuscitation (CPR) is considered an aerosol-generating procedure. Consequently, COVID-19 resuscitation guidelines recommend the use of personal protective equipment (PPE) during resuscitation. In this simulation of randomised crossover trials, we investigated the influence of PPE on the quality of chest compressions (CCs). Thirty-four emergency medical service BLS-providers performed two 20 min CPR sequences (five 2 min cycles alternated by 2 min of rest) on manikins, once with and once without PPE, in a randomised order. The PPE was composed of a filtering facepiece 3 FFP3 mask, safety glasses, gloves and a long-sleeved gown. The primary outcome was defined as the difference between compression depth with and without PPE; secondary outcomes were defined as differences in CC rate, release and the number of effective CCs. The participants graded fatigue and performance, while generalised estimating equations (GEE) were used to analyse data. There was no significant difference in CC quality between sequences without and with PPE regarding depth (mean depth 54 ± 5 vs. 54 ± 6 mm respectively), rate (mean rate 119 ± 9 and 118 ± 6 compressions per minute), release (mean release 2 ± 2 vs. 2 ± 2 mm) and the number of effective CCs (43 ± 18 vs. 45 ± 17). The participants appraised higher fatigue when equipped with PPE in comparison to when equipped without PPE (p < 0.001), and lower performance was appraised when equipped with PPE in comparison to when equipped without PPE (p = 0.031). There is no negative effect of wearing PPE on the quality of CCs during CPR in comparison to not wearing PPE.