Ablation at wavelengths near λ = 6.45 μm results in tissue ablation with minimal collateral damage (<40 μm) yet yields a high ablation rate that is useful for human surgery. However, delivery of this wavelength has been limited to that in air and thus to applications in which the target tissue can be readily exposed. The goal of this study is to investigate the potential of a pulsed infrared laser at λ = 6.45 μm for noncontact ablation in a liquid environment. To this end we investigated fiber delivery in combination with the use of infrared transparent liquids. Transmission characteristics and damage thresholds for two types of fiber materials (silver halide and arsenic sulfide), for high-power pulsed laser radiation were determined using the Mark III free electron laser. Both fibers had comparable bulk losses (0.54 dB/m and 0.62 dB/m, respectively) while the arsenic sulfide fibers showed more coupling losses (37 versus 27%). Damage thresholds were higher in arsenic sulfide fibers than in silver halide fibers (1.12 GW/cm2 versus 0.54 GW/cm2), but both fibers were sufficient to deliver radiant exposures well above the ablation threshold in tissue. Seven different perfluorocarbon liquids (PFCLs), known for their transparency at λ = 2.94 μm, were investigated and their optical transmission was determined using Fourier transform infrared and direct Beer's law measurements. All of the PFCLs tested had similar values for an absorption coefficient μa at a given wavelength (μa = 0.05 mm–1 at λ = 2.94 μm and μa ~3 mm–1 at λ = 6.45 μm). Pump-probe imaging showed the ablation sequence (λ = 6.45 μm) at the fiber tip in a water environment, which revealed a fast expanding and collapsing bubble. In contrast, the volatile PF-5060 showed no fast bubble expansion and collapse, but rather formation of nontransient gas bubbles. Perfluorodecalin did not show any bubble formation at the radiant exposures used. It was shown that using the λ = 6.45 μm wavelength delivered via fiber optics in combination with perfluorodecalin allows a noncontact laser surgical procedure. Deeper structures, however, are effectively shielded because the radiant exposure of the beam will fall below the ablation threshold owing to the absorption by perfluorodecalin. This may optimize the efficacy and safety of laser-based vitreoretinal surgery.