The purpose of the study is to investigate if metabolic syndrome (MS) and other comorbidities are associated with Peyronie's disease (PD).A total of 1833 patients retrospectively investigated and divided into two groups: Group A - PD patients ( = 319) and Group B - non-PD patients ( = 1303). The two groups were fully evaluated for diabetes mellitus (DM) with the glycated hemoglobin (HbA1c), hypertension (HTN), dyslipidemia (DL), obesity by measuring body mass index, total testosterone (T), penile vascular circulation measuring Peak systolic velocity (PSV) as indicator of arterial supply, end-diastolic velocity (EDV) as indicator of venous output, and finally, smoking.The presence of diabetes was significantly correlated with PD ( = 0.005). Patients with diabetes had a 7% higher incidence of PD. However, patients with the highest HbA1c level of >8.5 had an increased odds ratio of 1.6 ( = 0.025, confidence interval [CI] =1.061-2.459) of having PD. Increased age was significantly correlated with PD ( = 0.025). For each year of life, the likelihood of having PD increases by an odds ratio of 1.019, or 2% per year ( = 0.001, CI = 1.004-1.027). Unexpectedly, DL ( = 0.006) and smoking ( = 0.041) were associated with lower incidences of PD. Patients with DL or smoking had a 5%-7% lower incidence of PD with an odds ratio of 0.6 ( = 0.006, CI = 0.410-0.864). HTN ( = 0.621) and the total number of comorbidities ( = 0.436) were not correlated with PD. Mean serum T values were statistically ( = 0.43) but not clinically significant among patients with Peyronie's versus patients without Peyronie's (4.62 vs. 4.38 ng/ml). Neither low PSV (Fisher's exact test = 0.912) nor abnormal EDV (Fisher's exact test = 0.775) was correlated with the finding of PD.While MS was not associated with PD, diabetes, particularly poorly controlled diabetes, was associated with an increased rate. Further research into the interaction of PD and metabolic disease is warranted.