OBJECTIVE To assess knowledge regarding adherence and safety of oral contraceptive pills (OCP) in Saudi women. METHODS We conducted a cross-sectional prospective study in an outpatient pharmacy at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from April to September 2011. Participants were healthy women aged greater than or equal to 18 years with an OCP prescription for contraception. We used a validated questionnaire to assess their knowledge regarding adherence and safety of OCPs. RESULTS Four hundred and sixty women participated. Most (79%) knew to take an extra pill if they missed one in less than 12 hours, but only 6.5% knew they also had to use extra protection for the next 7 days if it was more than 12 hours. Multiple logistic regression analyses indicated that years of contraceptive use and educational level are predictive factors of better knowledge regarding adherence. Few were aware of the action if they experienced diarrhea for more than 12 hours (10%) or vomiting within 2 hours (13.5%) of taking an OCP. Only 30% knew of the adverse effects of smoking while on OCPs. Weight gain (51%) was the most commonly reported side effect. CONCLUSION Most Saudi women taking OCPs have limited knowledge of its correct use regarding missing pills, vomiting and diarrhea, and poor awareness of the effects of smoking while using OCPs.