OBJECTIVES: Generic medicines are one of the main avenues for reducing health care spending by all payers. There are no clear guidelines for generic and brand substitution in Saudi Arabia’s community pharmacies. We assessed knowledge, attitude, perception, factors and current practices among community pharmacists towards generic medicines substitution in Saudi Arabia.METHODS: A cross-sectional study was conducted between November 2017 to January 2018 including licensed community pharmacists from different regions in Saudi Arabia. A 38-item validated self-completed questionnaire, the data were analyzed using SPSS, and descriptive statistics were applied.RESULTS: Out of 1928 responses, 75.8% believed that pharmacists are allowed to change between generic and brand medications without consulting physicians. Almost 30 % believed that generics are less effective than brands. Almost 55.8% of participants support generic substitution where generic is available. However, 67% thinks that promotional activities by pharmaceutical companies plays important role in choosing the dispensed generic product. Generally, 35 % of pharmacists believe they would dispense generic products for their clients. However, 29% believed they would not. The main reasons pharmacists cited for not consulting the physician before substitution was the over the counter drugs (78%), and unavailability of physicians' contact numbers (54%). The two most common reasons for recommending generics were patient demand and cost (79%, 78% respectively). CONCLUSIONS: The community pharmacists knowledge and perception about generic medicines were somehow limited and needs improvement. Patients demand and marketing activities influences the substitution decision. There is a need to implement polices to improve proper use and awareness generic medicines in Saudi Arabia.