The aim of the present work was the development and application of a methodology for the safety assessment of chemical plants based on LOPA (Layer of Protection Analysis) techniques. The approach integrates the use of consolidate hazard identification techniques (HazOp) and the adoption of quantitative literature models for consequence assessment (e.g., integral models) into the LOPA framework, allowing to limit the role played by expert judgment in the evaluation in order to reduce the causes of uncertainty in the results. Furthermore, a systematic and quantitative assessment of safety measures contribution to the reduction of plant residual risk was included in the analysis. In order to apply the methodology, a case study was defined taking into account an actual industrial facility. The results obtained allowed demonstrating the potentialities of the method.