Abstract: Purpose: The purpose of this study is to validate the PenRed Monte Carlo framework for clinical applications in brachytherapy. PenRed is a C++ version of Penelope Monte Carlo code with additional tallies and utilities. Methods and materials: Six benchmarking scenarios are explored to validate the use of PenRed and its improved bachytherapy-oriented capabilities for HDR brachytherapy. A new tally allowing the evaluation of collisional kerma for any material using the track length kerma estimator and the possibility to obtain the seed positions, weights and directions processing directly the DICOM file are now implemented in the PenRed distribution. The four non-clinical test cases developed by the Joint AAPM-ESTRO-ABG-ABS WG-DCAB were evaluated by comparing local and global absorbed dose differences with respect to established reference datasets. A prostate and a palliative lung cases, were also studied. For them, absorbed dose ratios, global absorbed dose differences, and cumulative dose-volume histograms were obtained and discussed. Results: The air-kerma strength and the dose rate constant corresponding to the two sources agree with the reference datatests within 0.3% (Sk) and 0.1% (K). With respect to the first three WG-DCAB test cases, more than 99.8% of the voxels present local (global) differences within +/- 1%(+/- 0.1%) of the reference datasets. For test Case 4 reference dataset, more than 94.9%(97.5%) of voxels show an agreement within +/- 1%(+/- 0.1%), better than similar benchmarking calculations in the literature. The track length kerma estimator scorer implemented increases the numerical efficiency of brachytherapy calculations two orders of magnitude, while the specific brachytherapy source allows the user to avoid the use of error-prone intermediate steps to translate the DICOM information into the simulation. In both clinical cases, only minor absorbed dose differences arise in the low-dose isodoses. 99.8% and 100% of the voxels have a global absorbed dose difference ratio within +/- 0.2%for the prostate and lung cases, respectively. The role played by the different segmentation and composition material in the bone structures was discussed, obtaining negligible absorbed dose differ-ences. Dose-volume histograms were in agreement with the reference data.Conclusions: PenRed incorporates new tallies and utilities and has been validated for its use for detailed and precise high-dose-rate brachytherapy simulations.