Welding fumes have been found to be carcinogenic and stainless steel welders may be at higher risk due to increased formation of hexavalent chromium (Cr(VI)). The slag-shielded methods, identified to generate most airborne particles and Cr(VI), would potentially be most harmful. With ever-stricter limits set to protect workers, measures to minimize human exposure become crucial. Austenitic stainless steel flux-cored wires of 316L type have been developed with the aim to reduce the toxicity of the welding fume without compromised usability. Collected particles were compared with fumes formed using solid, metal-cored, and standard flux-cored wires. The size, morphology, and composition were characterized with scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). Total metal concentrations and released amounts of metals (Cr, Cr(VI), Ni, Mn, Fe) were investigated after complete digestion in aqua regia and after incubation in phosphate buffered saline (PBS) by means of flame furnace atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectroscopy (ICP-MS), and UV–vis spectroscopy. The cytotoxicity of the particles was assessed with the Alamar blue assay for cell viability using cultured human bronchial epithelial cells (HBEC-3kt). The findings correlate well with previous in vitro toxicity studies for standard and experimental wires. The new optimized 316L-type flux-cored wires showed improved weldability and generated less Cr(VI) in wt.-% than with solid wire. The respirable particles were confirmed to be less acute toxic in HBEC-3kt cells as compared to standard flux-cored wires. The highest cell viability (survival rate) was observed for the metal-cored wire.