BACKGROUND: Laser tattoo removal conventionally uses Q-switched (QS) lasers, but they require multiple sittings, and the end results depend largely on the type of tattoo treated. In pigmented skin, due to the competing epidermal pigment results, laser results in tattoo are slow and inadequate. OBJECTIVE: To evaluate the efficacy of a combined use of ultrapulse CO2 and QS Nd:YAG (1064 nm) laser in the treatment of tattoos in Indian skin. MATERIALS AND METHODS: A split-lesion trial was carried out in five patients, with the left side of tattoos receiving the QS Nd:YAG (1064 nm) and the right side, a sequential combination of Up CO2 and QS Nd: YAG at 6 weeks interval with a maximum of six sittings. Outcome assessment was carried out by a blinded assessor using standardized photography. An assessment of physician improvement score, side-effects score, and patient satisfaction score was taken during and at the end of the study. RESULTS: There was a statistically significant improvement on the combination side(physician improvement score -3.7 vs. 1.87: P = 0.0019) which occurred earlier with fewer sittings (1.7 vs. 6). There was no statistically significant difference in the side effects. CONCLUSION: A combination of an Up CO2 laser with QS Nd: YAG laser is a promising tool for rapid and effective removal of blue-black/blue amateur tattoo in pigmented skin.