During femtosecond (fs) laser ablation, fumes with remarkably low emission mass rates compared to conventional laser processes are generated. In this case the size of particles released in the workplace is relatively small, in the range of 10 nm–1 μm. The high amount of inhalable particles generated during femtosecond laser ablation has to be considered as a potential health risk, demanding quantification. In order to provide safety-related statements on nonbeam hazards during laser materials processing, the particle size distribution during femtosecond laser ablation is studied. Possible effects on this distribution like the laser parameters, materials, and the process atmosphere are examined. The mass flow rate and aerodynamic particle size distribution during femtosecond laser ablation were studied for metals (Ti, Co, Ag, Au, Mg), ceramic (ZrO2), and organic (polycarbonate, paper, graphite) materials. In addition, the influence of laser and process parameters (fluence, pulse overlap, gas atmosphere) on the particle size distribution has been investigated. At typical laser parameters (50 μJ, 1 kHz, 150 fs) used for microstructuring, the emission mass rates for nine different target materials are in the range of 5–120 mg h−1, and the share of nanoparticles varies from 10\% to 99\% depending on material and laser parameters. A maximum particle generation rate, defined as number of particles generated per pulse per centimeter squared, of 108 cm−2 has been observed, which is 100 times higher compared to Nd:yttrium-aluminum-garnet laser ablation. The nanoparticle number concentration in the ablation chamber is in the range of 104–106 per cm3, the generation rate amounts to 108 particles per second. The particle surface area of biopersistent particles has been calculated in a worst-case scenario and compared to nanoparticle toxicity indicators from literature. The amount of the fs-laser generated particle surface area (1 cm2 per day) is negligible compared to the thresholds of an inflammatory response in the animal model (200 cm2 of total nanoparticle surface per cm2 lung surface area). But within one laser manufacturing shift, the generated nanoparticles may accumulate in the workplace to a number concentration which is 200 times higher than the background concentration. We have used laser parameters which are commonly reported in literature. For the risks assessment during high-productivity processes, it has to be considered that femtosecond lasers available today deliver beams with an average output power of 5–50 times higher than that applied in this investigation. There is no standard or regulation effective today with definitions based on the size of particulate process by-products, so that the design of a laser ablation system is not restricted by the share of nanoparticles released by this machinery. The calculation of the nominal hygienic air requirement limit values and the nominal air volume flow rate shows that the process is safe with regards to nonbeam hazards for any of the studied materials if air exchange rates higher than 3 h−1 are applied (e.g., 150 m3/h for a typical 50 m3 lab). Despite the potential risk of the generated nanoparticles, the described method may also be quite useful for the production of well-defined nanoparticulate reference materials for toxicology studies in the future.