Background: Urolithiasis is one of the most common diseases of the urinary system, the incidence of which is assumed to be up to 100,000 cases per million (10% of the population). The cause of it is dysregulation of renal urine excretion. Acromegaly is a very rare endocrine disorder that causes a somatotropic pituitary adenoma producing higher amounts of growth hormone. It occurs approximately in 80 cases per million (about 0.008% of the population). One of the acromegaly complications may be urolithiasis. Methods: Clinical and laboratory results of 2289 patients hospitalized for nephrolithiasis in the highest reference hospital were retrospectively analyzed, distinguishing a subgroup of patients with acromegaly. Statistical analysis was performed to compare the prevalence of the disease in the analyzed subgroup with the epidemiological results available in up-to-date literature. Results: The distribution of nephrolithiasis treatment was definitely in favor of non-invasive and minimally invasive treatment. The methods used were as follows: ESWL (61.82%), USRL (30.62%), RIRS (4.15%), PCNL (3.1%), and pyelolithotomy (0.31%). Such a distribution limited the potential complications of the procedures while maintaining the high effectiveness of the treatment. Among two thousand two hundred and eighty-nine patients with urolithiasis, two were diagnosed with acromegaly before the nephrological and urological treatment, and seven were diagnosed de novo. Patients with acromegaly required a higher percentage of open surgeries (including nephrectomy) and also had a higher rate of kidney stones recurrence. The concentration of IGF-1 in patients with newly diagnosed acromegaly was similar to those treated with somatostatin analogs (SSA) due to incomplete transsphenoidal pituitary surgery. Conclusions: In the population of patients with urolithiasis requiring hospitalization and interventional treatment compared to the general population, the prevalence of acromegaly was almost 50-fold higher (p= 0.025). Acromegaly itself increases the risk of urolithiasis.