Background: Many governments encouraged generic use to enhance health equality and minimise health expenditure. The lack of knowledge and acceptance of generic medicines are the main barriers to their use. Objectives: This study aimed to assess population knowledge and perception towards generic drugs, identify their primary sources of information and examine which variables are independently related to their acceptance. Design: An observational cross-sectional study was performed targeting the Lebanese adult population. Methods: Overall, 385 patients participated in the study. Data were collected using a uniform survey from six public healthcare centres. Results: The participants reported a distrust towards generic drugs; they either said that they were not as effective as the brand (36.9%), were of less quality than the brand (38.5%) or had more side effects than the brand (38.4%). Around 52% said they would never buy a generic drug, and two-thirds (68.6%) preferred using a brand drug over a generic one. After adjusting for socio-demographics, a high income (odds ratio (OR) = 3.7), knowing that brands and generics have the same active ingredients (OR = 2.28) and that brands and generics were equally effective (OR = 6.46) were the strongest independent predictors for the willingness to buy generic drugs. Conclusion: A lack of knowledge and misperceptions about generic drugs limited the use of generic drugs, and therefore must be addressed.