Analysis of the different methods of teaching English has become increasingly important as the subject of global Englishes receives greater attention. In Asia, more educators have been using textbooks that are culturally specific in their design; however, a limited number of studies have been conducted that demonstrate their practical efficacy. Building on a preliminary study into the effectiveness of culturally familiar materials in EFL education in Japan, a crossover study using both quantitative and qualitative methods was conducted to examine the influence of cultural familiarity on university students' reading comprehension, vocabulary retention, and interest in the texts. Seventy-eight lower-intermediate level EFL students from four intact classes were divided into two groups with equivalent vocabulary proficiency. Participants read four simplified newspaper articles that contained culturally familiar or unfamiliar proper nouns allocated using a crossover design. Pre- and post-lesson tests were used to gauge the effectiveness of culturally familiar proper nouns on reading comprehension, vocabulary retention, and interest of each article. The results revealed that students who read the culturally familiar version of the articles scored higher in reading comprehension and vocabulary retention, and generally reported greater interest and engagement. These findings provide important insights to EFL educators, learners and material designers.