Lafutidine was subjected to forced degradation under the conditions of hydrolysis, oxidation, thermal and photolysis, in accordance with ICH guidelines Q1A(R2) and Q1B. Thirteen non-volatile and one volatile degradation products (DPs) were formed under different stress conditions. Among them, DPs IV, V, VII and IX were formed under acidic stress conditions, while DPs I, X and XIII were formed upon basic stress. Oxidative stress resulted in the generation of DPs II, III and VI. DPs XII and XIII were formed under photoacidic condition, while DPs VIII and XI were formed under both photoacidic and photoneutral conditions. The single volatile DP was formed only on acidic stress. In order to characterize the non-volatile DPs, complete mass fragmentation pathway of the drug was established with the help of MS/TOF and MS n studies, followed by LC-MS/TOF and on-line H/D exchange experiments. Twelve out of thirteen non-volatile DPs were characterized successfully. Structure of DP-I could not be elucidated, as it did not ionize in both ESI and APCI modes. The lone volatile DP was characterized using GC-MS data and correlation with mass information in NIST library. Finally, degradation pathway and mechanisms for the formation of the DPs were postulated.