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Objectives: This study aimed to explore high school students' awareness and attitude towards premarital screening (PMS)., Methods: This cross-sectional study was conducted in 10 public high schools in Muscat, Oman from May to July 2016. A three-part self-administered questionnaire was used to collect data from grade 12 students. The first part focused on respondents' sociodemographic characteristics, while the second part dealt with awareness of the national PMS programme and the third part explored attitudes towards the national PMS programme., Results: A total of 1,541 participants (response rate: 91.1%) completed the questionnaire. Most participants (78.1%) were aware of the availability of the PMS programme and their main source of information was family and friends (34.3%). The majority of students (87.4%) believed that PMS is important and most students (87.2%) indicated that they would undergo PMS. Over half of the students (55.3%) agreed that PMS should be mandatory before marriage and approximately one-third (38.3%) were in favour of having laws and regulations to prevent consanguineous marriages. Females were significantly more in favour of making PMS mandatory ( P = 0.002) and enforcing PMS laws ( P = 0.010) compared to males., Conclusion: Most respondents had good levels of knowledge about the PMS programme and half thought it is important to be tested. However, some students were not in favour of PMS. Increasing awareness about Oman's PMS programme is important and motivating students could contribute significantly to increasing the utilisation of the PMS programme and to limiting genetic blood disorders., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest., (© Copyright 2019, Sultan Qaboos University Medical Journal, All Rights Reserved.)