Suboptimal knowledge on medication use and safety and negative attitudes has negative impact on drug use. The major objective of this study was to measure the public knowledge and to identify their attitudes and practices on medication use and safety. Two cross –sectional surveys (Public-based and internet-based) were conducted during June to October 2015. Adult (> 18 years old) Saudi residing in Taif City; KSA were included. Convenience method of sampling was adopted and data was collected by mean of a structured questionnaire. Data was processed by SPSS. A total of 788 (386 and 402 in the public-based and the internet-based study, respectively) was recruited. Respondents recruited electronically with satisfactory knowledge on medication use were 302 (75.1%), compared to 234 (60.6%) included manually, (P= <0.001). Predictor of satisfactory knowledge among public survey interviewees was higher education [OR= 1.9; 95% CI (1.2-2.9); P = 0.003]. However, age (> 30 years) and higher educational level were significantly associated with satisfactory knowledge among electronically responded participants [OR= 0.6; 95% CI (0.4-1.0); P = 0.032] and [OR= 1.9; 95% CI (1.1-3.2); P = 0.015], respectively. Misconceptions in knowledge, attitudes and practices on medication use and safety were identified. Public education that brings about positive changes is imperative