Background and Objectives: Multiple treatments of resistant tattoos often result in fibrosis and visible textural changes that lessen response to subsequent treatments. The aim of this study is to evaluate the influence of beam profile and spot size on clearance rates and side effects in the setting of resistant tattoos. Study Design/Material and Methods: Thirty-six professional, black tattoos (32 patients) were treated unsuccessfully with a Q-switched Nd:YAG laser (MedLite TM C3, HoyaConBio Inc., Fremont, CA). Because of therapy resistance all tattoos were re-treated using a new generation Nd:YAG laser (MedLite TM C6, HoyaConBio Inc.). Maximum energy fluence (E max ), mean energy fluence, mean spot size, level of clearance, side effects and beam profile (irradiance distribution) of both laser systems were assessed and evaluated in a retrospective study. Results: All tattoos were previously treated with the C3 laser at 1,064 nm using a mean E max of 5.8 AE 0.8 J/cm 2 (range 3.8-7.5 J/cm 2 ) as compared with a mean E max of 6.4 AE 1.6 J/cm 2 (range 3.2-9.0 J/cm 2 ) during the C6 treatment course. Corresponding spot sizes were larger during C6 treatments as compared with C3 (5.0 AE 0.9 and 3.6 AE 0.2 mm, respectively). The C6 laser had a ''flat top'' and homogenous profile regardless of the spot size. For the C3 laser the beam shape was ''Gaussian,'' and the homogeneity was reduced by numerous micro-spikes and micro-nadirs. After the C6 treatment course 33.3% of the tattoos showed clearance of grade 1 (0-25%), 16.7% of grade 2 (26-50%), 16.7% of grade 3 (51-75%), 30.5% of grade 4 (76-95%), 2.8% of grade 5 (96-100%). The total rate of side effects due to C6 treatment was 8.3% in all tattoos (hyperpigmentation 5.6%, hypopigmentation 2.7%, textural changes/scars 0%). Conclusion: This clinical study documents for the first time the impact of a 1,064-nm Nd:YAG laser with a more homogenous beam profile and a larger spot size on the management of resistant tattoos. Only a few treatment sessions were necessary to achieve an additional clearance with a low rate of side effects.