Recent incidents involving chemical, biological, radiological and nuclear substances have stressed the importance of sufficient personal protection equipment for medical first-responders. Modern lightweight, battery-independent, suit ensembles may prove superior to the current protective suit used in the UK. This study compared the powered respiratory protective suit (PRPS ensemble) with a lightweight suit consisting of a SARATOGA Multipurpose CBRN Protective Coverall Polyprotect 12 in conjunction with the Avon C50 Respirator/Avon CBRNF12CE filter canister and butyl rubber protective gloves (Polyprotect 12 ensemble). Thirty anaesthetists carried out a standardised resuscitation scenario either unprotected (control) or wearing the PRPS or Polyprotect 12 ensembles in a randomised, crossover simulation study. Treatment times for five simulated advanced life support interventions (application of monitoring; bag/mask ventilation; tracheal intubation; drug and fluid administration; and external pacing) were measured. Wearer comfort was also assessed for the two protective suits by questionnaire. All participants accomplished the treatment objectives of all study arms without adverse events. Total mean (SD) completion time for the five interventions was significantly longer for the PRPS compared with the Polyprotect 12 ensemble (204 (53) s vs. 149 (36) s, respectively; p < 0.0001). Participants rated mobility, noise, heat, vision, dexterity and speech intelligibility significantly better in the Polyprotect 12 ensemble compared with the PRPS ensemble. The combination of a lightweight Polyprotect 12 suit and an Avon C50 air-purifying respirator is preferable to the powered respiratory protective suit during simulated emergency life support, due to a combination of shorter task completion times and improved mobility, communication and dexterity.