Several studies describing the “natural history” of Peyronie’s disease Chronic Inflammation of the Tunica Albuginea-CITA) showed that untreated patients with PD seem to have spontaneous improvement. Because of these articles many physicians found to have a non-therapeutic behavior in case of PD. This paper tries to define the natural history of PD using penile dynamic duplex ultrasound evaluation in function of factors able to elicit fibrosis of the penis. Eighty-two patients have been studied, the mean time being between PD onset and diagnosis was 9.6 ± 3.8 months, mean age was 52.6 ± 10.69. Each patient underwent to two clinical assessments for PD, with a time-lag of 18.08 ± 9.2 months. Each assessment comprises: measurement of: plaque volume in cm3 (with dynamic echocolor Doppler ultrasonography), penile curvature in degrees (with Kelami method), pain (with Pain Intensity Numerical Rating Scale/PINRS) and sexual function (with IIEF15 scale). The following clinical and laboratory assessments were carried out on each patient: body-mass index (BMI), blood pressure measurement, blood count, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, blood sugar, glycated haemoglobin and total testosterone. We assessed whether PD plaque volume, penile deformity, pain and modify by time, in function of risk factors of fibrosis (aging, smoking habit, erectile failure, number of comorbidities, BMI, radical prostatectomy) and/or of the severity of symptoms (plaque area, penile deformity and calcifications). Qualitative-quantitative non parametric multivariate analysis has been used as statistical test. The analysis indicated that PD symptoms increase by time in the majority of the patients, and that the increase is not linked to the severity of symptoms, but to the risk factors for developing fibrosis, with the exception of age that is inversely related. PD is a progressive disease, whose progression is linked to young age and to risk factors of fibrosis.