OBJECTIVES: Recently, there is growing evidence of inappropriate variation in use of certain medicines. In Serbia the consumption of pentoxifylline, dihydroergotoxine, nicergoline, deproteinized calf blood extract (DCBE) and cinnarizine, drugs with uncertain clinical benefit (UCB drugs), with clinical trials with little evidence suggesting their clinical benefit, is unusually high. The aim of this study was to analyze the consumption of UCB drugs in second largest city in Serbia – Novi Sad, in 1984 and 2008., to compare with those in entire Serbia, Denmark and Norway, and to examine the potential impact on population budget. METHODS: The study included data on consumption of these medicines in 1984. and 2008., in Novi Sad. Data were obtained from all state-owned and private pharmacies on the territory of Novi Sad. The number of  (DDD/1000 inh/day) was calculated using ATC/DDD methodology. RESULTS: Total consumption of analyzed drugs with uncertain clinical benefit in Novi Sad has surprisingly increased in 2008 (12,59DDD/TID) in comparison to 1984 (7.37DDD/TID). Also, their total consumption in entire Serbia in 2008. was higher than in Novi Sad (16,72DDD/TID) and even several dozens of times higher than in Denmark and Norway (0.2DDD/TID). The money which population spent for UCB drugs yearly was more than 90 Mill EU in Serbia Although different administrative and educational approaches were applied in Serbia, their use not only did not decrease, but has significantly increased throughout years. CONCLUSIONS: These results suggest the need for putting greater efforts into education of general population who buys the UCB medicines in high amounts on their own accord. The work is part of SerbianSP No41012