In recent years room temperature medium resolution scintillation devices, such as LaBr3(Ce), have attracted much interest as possible alternatives to traditional spectrometers based on HPGe and NaI detectors, for the determination of the uranium enrichment in safeguards applications. This paper focuses on the investigation of possibilities and limits of a net peak area based methodology used for the determination of the uranium enrichment without use of calibration standards and introduces the isotopic code MCSIGMA for LaBr 3(Ce) scintillators. Tests are conducted with a room temperature, medium resolution spectrometer based on a 2 ×2 inch LaBr 3(Ce) scintillator using which spectra of different statistical quality are obtained from certified uranium standards. Gamma peaks in the 143-1001 keV energy range are used as uranium gamma-ray signatures. Results indicate a promising performance of the applied methodology with a room temperature medium resolution scintillator of the LaBr 3(Ce) type, however at a cost of significantly higher uncertainty budget on the derived enrichment compared to HPGe, especially for natural and depleted uranium samples. This uncertainty budget is primarily influenced by the statistical quality of the measured spectra. Implemented algorithms and analysis routines are described in detail and presented.