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This article is from PLoS ONE , volume 9 . Abstract So far, many studies on educational games have been carried out in America and Europe. Very few related empirical studies, however, have been conducted in China. This study, combining both quantitative with qualitative research methods, possibly compensated for this regret. The study compared data collected from two randomly selected classes (out of 13 classes) under computer game-based instruction (CGBI) and non-computer game-based instruction (NCGBI), respectively, in a senior high school located in Nanjing, Capital of Jiangsu Province, in China. The participants were 103 students, composed of 52 boys and 51 girls (aged 17-18 years old). The following conclusion was reached: (1) participants under CGBI obtained significantly greater learning achievement than those under NCGBI; (2) participants were significantly more motivated by CGBI compared with NCGBI; (3) there were no significant differences in learning achievement between boys and girls; although (4) boys were significantly more motivated by CGBI than girls. Both disadvantages and advantages were discussed, together with directions for future research.