OBJECTIVES: Prescription drug prices between Canadian and US on-line pharmacies were studied over a 6-month period. METHODS: Prices for 28 popular brand name medications were collected from eight Canadian and five US on-line pharmacies weekly for six months. Prices were compared between Canadian and US on-line pharmacies, and price changes were monitored each week. RESULTS: During the study period, purchasing from Canadian on-line pharmacies would save consumers >$1.00 per unit for 12 drugs (42.9%). Savings were demonstrated in two drugs if purchased from US on-line pharmacies: sildenafil 25mg ($2.06/unit) and amlodipine 10mg ($0.02/unit). Average price increases from the first to the last week of the 6-month period were greater from Canadian on-line pharmacies ($0.10/unit) compared to the US ($0.07/unit). From Canadian on-line pharmacies, prices from all the medications increased during the study period except one, which stayed the same. The two drugs with the greatest price increases were alendronate 70mg ($1.04/unit) and sildenafil 25mg ($0.45/unit). From US on-line pharmacies, nine drug prices decreased during the study period, four remained the same, and 15 increased. The greatest price increases were for alendronate 70mg ($0.62/unit) and olanzapine 10mg ($0.41/unit). Consumer savings from purchasing Canadian on-line drugs decreased from the first to the last week of the 6-month period for 17 medications (60.7%), with the greatest decrease in savings being for 100 units of gabapentin 300mg (19.4% decrease) and sertraline 100mg (15.1% decrease). CONCLUSIONS: When 100% of prescription drug payments are out-of-pocket, consumers usually save money when buying from Canadian on-line pharmacies. Although prices were lower using these pharmacies, price increases over the study period were greater. In order to get the best price for medications purchased on-line, one would need to compare prices from multiple pharmacies in Canada and the US for each prescription drug over a period of time.