The purpose of this study was to evaluate the safety and efficacy of a new combined method of Q-S laser-assisted tattoo removal. Ten patients with 13 professional, mostly mono-chromatic black tattoos were recruited. All tattoos received the same Q-S laser treatment sequence. An objective evaluation of tattoo clearing was assessed by careful analysis of a standardized collection of digital images taken from each tattoo, 2 months after each laser session, with the help of a custom-made pigment-fading percentage photographic ruler. The percentages of pigment clearance and side effects were evaluated by 4 independent dermatologists. Patient satisfaction and perceived discomfort during and post-procedure were evaluated according to specific scales. Clinical evaluators confirmed an average photographic pigment clearance of 97% after a median 4.85 treatment sessions. The Frac-Tat® method required 40% fewer sessions compared to those calculated by Kirby-Desai estimates. Photographic assessment of laser-exposed skin quality performed 2 months after tattoo clearing was considered almost comparable with untreated peripheral skin, confirming a very low side effect score. The Frac-Tat QS laser-assisted tattoo removal sequence used in our study showed a high degree of safety and efficiency, clearing exogenous pigments in a relatively few number of sessions. Preliminary ablative photo-acoustic fractional 1064-nm Q-S laser micro-drilling was considered an essential step in optimizing tattoo removal, increasing wavelength-independent micro-columnar clearing of deeper dermal exogenous pigments. Our preliminary observations also confirmed a significant improvement of tattoo procedure-induced micro-textural changes thanks to a tissue remodeling effect induced by the 1064-nm Q-S fractional laser photo-acoustic ablation.