With the limited number of trained healthcare providers in Nigeria, patent and proprietary medicine vendors are inevitable and highly needed especially, in the rural areas for the supply of drugs to treating minor illnesses. The study assessed the knowledge, attitude, and practice of patient referral among patent and proprietary medicine vendors in an area with a limited hospital infrastructure. This cross-sectional descriptive survey was conducted in Obio-Akpor, Rivers State, Nigeria, using a semi-structured questionnaire that measured the participants’ socio-demographic characteristics as well as knowledge, attitude and practice of patient referral. Descriptive and inferential analyses were conducted with SPSS version 25. The majority of the respondents had moderate knowledge, attitude, and practice (62.4%, 73.4%, and 58.0%, respectively) of patient referral. Multivariate analysis carried out to ascertain the relationship between patent and proprietary medicine vendors background characteristics and level of knowledge, attitude, and practice of patient referral showed a significant inverse relationship between years of experience and odds of having the attributes of interest. Patent and proprietary medicine vendors with three years of experience reported significantly higher odds of adequate knowledge (AOR=178.96; 95% CI=60.15-532.49; p<0.005), attitude (AOR=07.38; 95% CI=03.78-14.40; p<0.005) and practice (AOR=131.56; 95% CI=53.50-323.51; p<0.005) than those with above 10 years of experience after controlling for the effects of other variables. The study showed that most respondents have moderate knowledge, attitude, and practice of patient referral. The respondents were aware of how referrals affected their clients' overall treatment outcome, but they also highlighted factors that confine their referral practices making them suboptimal.