Laser hair removal (photoepilation) is one of the most sought-after techniques in the field of aesthetic medicine. Although photoepilation techniques are constantly advancing, there is still a lot of scope for improvement in order to guarantee efficacy and the safety of the subject, especially for people with thinned hair and those with dark skin. We compared two pieces of diode laser photoepilation equipment (Soprano XL and Primelase Excellence), and the results obtained were compared with simulations made by a mathematical 3D simulation of hair and skin heating and thermal damage developed by Cocoon Medical, using COMSOL Multiphysics® software. Our results show that high-power Primelase equipment (up to 4800 W) increases the effectiveness of photoepilation treatments. After three treatments, the average hair reduction was 53% with Soprano XL and 69% with Primelase Excellence, which represents a 55% greater efficacy with primelase. Thermal simulations revealed that untreated or original hair showed very similar results for Soprano XL and Primelase Excellence, but simulations of thinned hair as it appears in treated areas showed significant differences between the two lasers, with an average improvement of 65% for Primelase Excellence for the cases analysed in this study. This improvement is due to the shorter laser pulses of Primelase which are in turn due to its greater power and to the possibility of using a multi-wavelength blend diode laser with higher fluences under safe conditions for dark skin types, which provides greater energy delivery to the hair follicles for all skin types. Nevertheless, neither system achieved permanent hair removal in three treatments. Additional photoepilation treatments and long-term results evaluation would need to be performed. In conclusion, this clinical study corroborates the results of the simulations which predict that the Primelase system is more effective for thin hair using comparable or lower energies and shorter pulses than the Soprano system, and using a blend diode laser for the darker skin types.