Polymeric materials (EPDM, NBR, CR, FKM, POM, PTFE, and others) are widely used in oxygen systems. During some technical operations, polymers might be exposed to temperature loading, for example, from a fast-opening valve, friction, or exposure to an elevated ambient temperature. Multiple standards are devoted to the evaluation of nonmetallic materials in oxygen service using different test methods. Although these standards are of great value with respect to safety, they do not address the scientific explanations behind the noncompatibility of the materials to oxygen. Even if organic materials are continuously used at moderate temperatures, the possible physicochemical changes induced by thermal oxidation may change their ignition resistance. This study focuses on one type of elastomer that is extensively used in many oxygen systems: polychloroprene (neoprene), which is an elastomer with good elastic and sealing properties and is known to be sensitive to oxidation. Fire resistance was studied using a laser source for localized and momentary energy deposition, and tools such as thermal and high-speed cameras were used to monitor the material changes and material temperature during ignition genesis and combustion in a pressurized oxygen environment. Since the laser allows the amount of energy to be delivered more flexibly and accurately, the ignition time can be determined more precisely and the energy delivered can be tailored to simulate field conditions. The study is broken down as follows: First, to simulate advanced degradation, we show the effect of thermo-oxidative aging under air, performed in an oven at 80°C to 100°C, on fire resistance. Second, we describe the relationship between the ignition behavior and the effect of the formulation and the aging (including on-site exposure), with a particular focus on the plasticizers (oils) used to facilitate processing.