The aim of this study was to evaluate the efficacy and long term safety of once daily administration of phenylpropanolamine (PPA) in the treatment of urethral sphincter mechanism incompetence (USMI) in spayed bitches in comparison to three times daily administrations. For this purpose, 22 spayed bitches suffering from USMI received either PPA at the dose rate of 1.5 mg/kg, body weight (BW) once daily (group I, n=11) or 1.5 mg/kg three times daily (group II, n=11) by oral administration. Clinical efficacy was determined by using a scoring system based on analysing the frequency and the amount of unconscious urination on d 7, 14 and 28. There was no significant difference (p>0.05) between the clinical response observed on d 7, 14 and 28 of treatment in group I and II. Eight dogs (72.7%) in each group were continent on d 28. The side effects observed were mild and transient. Phenylpropanolamine therapy was continued in 13 dogs that became continent after 28 d and the dogs were followed up for 12 months. None of the dogs showed symptoms of urinary incontinence except for 2 bitches that became refractory to PPA treatment in group II. Phenylpropanolamine was combined with estriol for 14 d (1 mg/dog PO) in dogs in which PPA therapy was inefficient or unsatisfactory on d 28 and in dogs that became refractory to PPA treatment. A total of 8 dogs were treated with estriol PPA combination. Five (62.5%) bitches were continent on 14th d of estriol PPA combination treatment. In one bitch (12.5%) urinary incontinence improved. In conclusion, once daily administration of PPA at a dose of 1.5 mg/kg, BW is effective in treatment of USMI in spayed bitches and it offers a cheap and convenient treatment option. In addition, recurrence of incontinence can be observed during long term administration of PPA and combination of PPA with estriol is effective in dogs in which PPA therapy alone is unsatisfactory and in dogs that become refractory to PPA treatment.