Purpose The purpose of this paper is to describe the prevalence and factors associated with safe sex behavior among vocational students in Nakhon Ratchasima Province, Thailand, and to determine the modifying factors listed as socio-demographic characteristic, the level of HIV and sexually transmitted infections’ knowledge, attitude toward reproductive health, and safe sex behavior among vocational students in Nakhon Ratchasima Province, Thailand. Design/methodology/approach A cross-sectional descriptive research was conducted from August to October 2018. The multistage stratified sampling, combined with purpose and random sampling, was used to select the participants. One vocational college with the highest number from urban, suburban and rural areas was purposely selected. The sample calculation by using Cochran’s formula, a random sampling by drawing from each college with male and female, was made to obtain the sample size of 355 students. Inclusion criteria included: vocational students, both male and female, aged between 15 and 19 years, resided in the study area, and volunteered to participate. Ethical consent including waiver of the parent’s consent for the participant aged under 18 years for this study was approved by the Institution Review Board for Human Research Ethics, Chulalongkorn University (Certification number JV 823/2561) A self-administered questionnaire was adapted by the principle researcher from the illustrative questionnaire for interview survey with young people (14), and The study of Prevalence of HIV, STD, Drug Use and Risk Behaviors in Adolescents and Young Adults, in Chaing Rai, Thailand (PRAYA) tool (15). All statistical analyses were performed by SPSS version 22. Findings The finding revealed that 332 participants were male (57.8 percent) and female (42.2 percent) with an average age of 16.8 years (±1.7). Approximately 60 percent of males and 50 percent of females had experience of sexual intercourse, with their first experience of sexual intercourse at the average age of 15. Most respondents 63.1 percent used a condom and 63.6 percent used contraception in their latest sexual intercourse. About 41.9 percent consumed alcohol and 15 percent reported substance abused. Sexual intercourse among adolescents vocational students were significantly associated with high knowledge of contraception (OR=0.30, 95%CI=0.10–0.82). Positive attitude toward reproductive health had a significant association with sexual intercourse (OR=0.17, 95%CI=0.05–0.58). Sexual intercourse among vocational students were also significant associated with low risk behavior (OR=0.45, 95%CI=0.22–0.91) and high risk behaviors (OR=0.24, 95% CI=0.10–0.59). Contraceptive used in the latest sexual intercourse had a significant association with cues to action (OR=0.43, 95% CI=0.22–0.86). Research limitations/implications This study used a self-reported questionnaire to collect information from participants about safe sex behaviors, which might contain bias data and socially desirable answers. The time for collecting data did not match vocational students’ schedule as they were about to have their final exams. An error in this questionnaire was the absence of condom use as one of the contraception methods. Practical implications The study showed that both male and female vocational students in Nakhon Ratchasima have a low level of knowledge of HIV, STIs and contraception. This study revealed that females have higher knowledge of all the factors more than males. Males usually received more harassment from peers for being sexually active than females do. Condoms and contraceptive used are inconsistent in all research conducted and have no common ground. Communication related to sex for those who have no partner was poor compared to students who have a partner. The four factors associated with safe sex behaviors should always be considered and surveyed among vocational students, as the study showed that all results vary for a future adolescence study. Social implications This research aims at government authorities. The policy makers should include reproductive health and rights in the curriculum. The Ministry of Public health and The Ministry of Education should provide training for the trainer program for teachers concerning safe sex behaviors. For future research, in-depth interview and qualitative study should be used to increase the reliability of the result of the inconsistency of using a condom and contraception. The researcher should do further studies into vocational college semester schedules before collecting data and should spend more time in the college, so the students become more acquainted to the researcher and give a more truthful answer. Moreover, condom use should be added as one of the contraception methods. Originality/value This is the first study among vocational students in Nakhon Ratchasima Province which emphasizes specifically on safe sex behaviors and factors related to it. Regarding the population of vocational students, this study covers almost 80 percent of the population. Sensitive questions for sexual activity status and sexually history were answered by a self-administered questionnaire in order to increase sincere answers on their experiences because participants were not shy to disclose their sexual experiences.