Background Research comparing the effects of culturally-targeted and generic but linguistically appropriate intervention programs is limited. We conducted a randomized controlled trial comparing the efficacy of a culturally-targeted video, a generic video, and a fact sheet (control) in promoting mammography screening among Chinese-American immigrants. Methods We randomized 664 Chinese-American women from the Washington, DC and New York City areas who were >40 years and non-adherent to annual mammography screening guidelines to three study arms (each with ~221 women). The outcome was self-reported mammography screening six months post intervention. Measures of knowledge, Eastern cultural views, and health beliefs were administered before and after the intervention. Results The culturally-targeted video, the generic video, and the fact sheet increased mammography utilization by 40.3%, 38.5%, and 31.1% from baseline, respectively. A significant intervention effect was observed only in one subgroup: The culturally-targeted video significantly increased mammography screening among low-acculturated women over the fact sheet (OR=1.70, 95% CI=1.04, 2.78). Overall, women who obtained a mammogram during the follow-up period reported significantly fewer barriers to screening after intervention than those who had not obtained screening. Both of the video groups reported fewer barriers after intervention than the control group. Conclusions Both theoretically-guided videos increased the likelihood of mammography use to a similar extent. Cultural targeting was only effective for low-acculturated women. Both videos reduced perceived barriers to screening and consequently increased screening behavior. Impact The results of this study provide empirical evidence on the efficacy of cultural targeting for minority immigrants.