Delivery of intradermally focused nanosecond laser pulses with small energy as an alternate technique applicable to clinical procedures in dermatological and plastic surgery is an area of relatively new interest with multiple potential applications. We assessed this approach on common tattoo pigments in dermis in an in vivo study using a wavelength of 1064 nm. Paired micropigs were tattooed with standard blue, black, green and red pigments. The tattoos were allowed to mature and then treated by 12 ns pulses in a focused beam of 11.4° cone angle. Visual observation and histological analysis of biopsies were performed to evaluate results. Significant reduction in pulse energy and collateral damage was achieved with pulse energy ranging between 38 to 63 mJ. Blue and black tattoos were found to respond well from a clinical standpoint. The depth dependence of tissue response and pigment redistributions at 1 hour, 1 week and 1 month after laser treatment was quantitatively analysed through biopsies and a strong relationship was demonstrated between tattoo response and laser-induced dermal vacuolation. The optical absorption coefficients of the four tattoo pigments were measured to be approximately the same and the laser-induced plasma is suggested to be responsible for the pigment redistribution. As we hypothesised, intradermal focusing of nanosecond pulses significantly reduced required pulse energy for tattoo ablation to about 60 mJ or less. These results stimulate a number of additional questions relevant not only to clinical applications but also to the understanding of the fundamental process of laser–pigment interaction in the dermis as it relates to tattoo removal.