The pathophysiology of nephrolithiasis is multifactorial. Obesity, diabetes mellitus and hypertension are implicated in its formation. Dyslipidemia (DLD) recently has received attention as well. Congruent with a vascular etiology in stone formation, DLD theoretically would predispose patients to nephrolithiasis. We investigated a possible association of DLD with nephrolithiasis. A random cohort of 60,000 patients was established by collecting the first 5,000 patient charts per month in the year 2000. After excluding pediatric patients, a retrospective study was performed by reviewing age, sex, comorbidities, and last patient follow-up. Median lipid laboratory levels also were reviewed. Descriptive statistics were performed as well as Cox proportional-hazards regression analysis, and univariate and multivariate analyses. 52,184 (22,717 women/29,467 men) patient charts were reviewed. The average age was 31.0 ± 15.2 years. On univariate analysis, DLD was associated with nephrolithiasis with a hazard ratio (HR) of 2.2 [Confidence Interval (CI), 1.9-2.5; p < 0.001] and on multivariate analysis HR = 1.2 (1.0-1.5; p = 0.033). Low-density lipoprotein and triglycerides had no association with stone disease. Patients with high-density lipoprotein (HDL) values <45 for men and <60 for women had an HR of 1.4 (1.1-1.7, 95% CI, p = 0.003) on univariate analysis and on multivariate analysis; HR = 1.27 (1.03-1.56; p = 0.024) for nephrolithiasis. DLD was associated with an increased risk of stone disease though the only specific lipid panel associated with lower nephrolithiasis was HDL. Clinicians should consider obtaining lipid levels with the intent that treatment could potentially not only mitigate atherosclerotic disease but also decrease nephrolithiasis risk.