Résumé : Room temperature semiconductor detectors of CdZnTe type have been proposed as possible alternatives to spectrometers based on HPGe and NaI detectors. Attractive spectroscopic performance and portability, as well as continuous improvements in their design and availability in different sizes make them especially competitive in various radiation measurement applications where absence of cooling, small size and significantly better resolution compared to other room temperature detectors are an asset. Among these applications are nuclear safeguards that include uranium and plutonium isotopic composition determination tasks. 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. Tests are conducted on a room temperature medium resolution spectrometer based on a 500 mm 3 CdZnTe sensor of a quasi-hemispherical design using which spectra of different statistical quality are obtained from certified uranium standards. Gamma-ray peaks in the 143–1001 keV energy range are used as uranium gamma-ray signatures. Performance assessment of an intrinsic calibration of the counting efficiency curve is conducted. A hybrid methodology based on a combination of the peak ratios method with Monte Carlo simulations of the counting efficiency curve is proposed for poor quality spectra. Implemented algorithms and analysis routines are described in detail and presented.