This research was studied the optimum conditions for sulfate removal from lignite coal mine drainage in Thailand by ettringite precipitation using Central Composite Design. The effects of Ca/S and Al/S ratio (mole basis), reaction time and temperature on the sulfate removal efficiency were investigated. The statistical analysis showed that the Al/S ratio and reaction time had a significant effect on sulfate removal efficiency. The sulfate removal efficiency increases when Al/S ratio and reaction time are increased. The Ca/S ratio in the range of 1–7 was found to have no significant effect on sulfate removal efficiency. The optimal reaction time obtained from the predicted equation was 6.14 h, while the Ca/S and Al/S ratios were fixed at 4 and 4.5, respectively, at ambient temperature. Under the optimum conditions, sulfate removal of 99.6 and 99.0% was achieved in both Lamphun and Lampang mine drainage, respectively, which is very close to the predicted value (100%). This study showed that the sulfate removal efficiencies of Lamphun and Lampang mine drainage sharply increased from 33.3 to 89.9% and 42.3 to 81.8%, respectively, when the temperature was increased from 25 to 80 ^○C during a 3 h reaction time. XRD results match well with a majority of ettringite and a minority of calcium carbonate when the precipitation was done at ambient temperature. However, monosulfate was found to be the majority when the precipitation was done at 80 ^○C due to the decomposition of ettringite to monosulfate at the high temperature.