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Background: Plantar hyperhidrosis is a common illness with significant impact on quality of life. Oxybutynin presents good short-term results, but longer follow-up results are lacking. We evaluated oxybutynin effectiveness in patients who were not surgically treated and who had at least six months of follow-up., Methods: From September 2007 to September 2013, 85 consecutive patients were enrolled in our institutional protocol for the "pharmacological-first" treatment of primary plantar hyperhidrosis with oxybutynin. Eight patients were lost to follow-up, 15 patients have not yet been under treatment for six months, and data were available for 39 patients (all female) treated for at least six months. Data at the start of the protocol, six weeks after beginning treatment, and at their final visit were analyzed., Results: Twenty-three of the 77 patients (29.87%) did not improve after pharmacological therapy. From the 39 patients with more than six months of follow-up (median 16.9 months, range 9-71), 79.5% reported moderate/great improvement in excessive plantar sweating after six weeks of treatment, and this rate increased to 84.7% in the last follow-up visit; 82.85% showed improvement in other sites presenting hyperhidrosis. Dry mouth was the most common side effect; 51.6% of patients reported it to be moderate/severe at the last visit., Conclusion: In patients with good initial response to oxybutynin, more than 82% presented moderate or great improvement in plantar and other sites' excessive sweating; dry mouth was the most common side effect but was tolerable and did not lead any patient to interrupt treatment., (© 2015 The International Society of Dermatology.)