The purpose of this study was to evaluate whether a comprehensive sexual education program for college students in Southwest China (a) improved sexual health knowledge in reproduction, contraception, condom use, sexually transmitted diseases, and HIV; (b) increased accepting attitudes toward lesbian, gay, bisexual, and transsexual individuals; and (c) altered participants’ attitudes toward premarital sex and monogamy. The program used diverse teaching methods, providing 6 sessions over a period of 9 weeks about sexual health knowledge and sexual attitudes to college students (age 18-26 years) in Southwest China. Sexual health knowledge and sexual attitudes of 80 comprehensive sexual education class students (education group) and 92 general mental health education class students (control group) were measured at baseline, the end of course (posttest), and 3 weeks after the end of course (follow-up). There were significant effects of the program on (a) sexual health knowledge, including reproductive health, contraception, condom use, and HIV/AIDS and (b) positive attitudes toward sexual minorities, although these changes may require further reinforcement. In contrast, the program did not alter students’ attitudes about premarital sex or monogamy. The results are discussed in terms of recommendations of sex education in China and future directions for research.