Surface modification processes are increasingly used to fully exploit material potential in fatigue critical applications because fatigue strength is sensitive to surface conditions. Nitriding is extensively adopted with ferrous materials because it forms a hard and strong surface layer and a system of superficial compressive residual stresses. Fatigue, however, is strongly dependent also on defects and inhomogeneity. When nitriding is applied to nodular cast iron, the relatively thin hardened layer (about 300 µm) contains graphite nodules (diameter of the order of 30 µm), casting defects and a heterogeneous matrix structure. The paper presents and discusses the influence of nitriding on the fatigue response and fracture mechanisms of nodular cast iron. A ferritic nodular cast iron and a synthetic melt with different content of effective ferrite were initially gas-nitrided. Then, (i) structural analysis of nitrided layers, (ii) fatigue testing with rotating bending specimens, and (iii) fatigue fracture surface inspection were performed. Performance and scatter in fatigue performance is discussed by selective inspection of fracture surfaces and identification fracture micromechanisms. A semiempirical model explains observed trends in test results and is used for the process optimization.