Aim To analyze clinical data from male patients treated with urethrotomy and to develop a clinical decision algorithm. Materials and methods Two large cohorts of male patients with urethral strictures were included in this retrospective study, historical (1985-1995, n=491) and modern cohorts (1996-2006, n=470). All patients were treated with repeated internal urethrotomies (up to 9 sessions). Clinical outcomes were analyzed and systemized as a clinical decision algorithm. Results The overall recurrence rates after the first urethrotomy were 32.4% and 23% in the historical and modern cohorts, respectively. In many patients, the second procedure was also effective with the third procedure also feasible in selected patients. The strictures with a length ≤ 2 cm should be treated according to the initial length. In patients with strictures ≤ 1 cm, the second session could be recommended in all patients, but not with penile strictures, strictures related to transurethral operations or for patients who were 31-50 years of age. The third session could be effective in selected cases of idiopathic bulbar strictures. For strictures with a length of 1-2 cm, a second operation is possible for the solitary low-grade bulbar strictures, given that the age is > 50 years and the etiology is not post-transurethral resection of the prostate. For penile strictures that are 1-2 cm, urethrotomy could be attempted in solitary but not in high-grade strictures. Conclusions We present data on the treatment of urethral strictures with urethrotomy from a single center. Based on the analysis, a clinical decision algorithm was suggested, which could be a reliable basis for everyday clinical practice.