Introduction Antiretroviral therapy has improved the life expectancy of patients living with HIV. However, lipodystrophy syndrome (LD) remains prevalent, affecting mostly patients treated with first-generation antiretroviral drugs. This syndrome is characterized by changes in body fat distribution with or without associated metabolic changes. Here, we studied whether clinically evaluated LD is independently associated with chronic kidney disease (CKD) development (sustained estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m) in HIV-positive patients. Methods We conducted a prospective cohort study (the LIPOKID Study) among all the patients from the Swiss HIV Cohort Study (SHCS) with an eGFR >60 ml/min per 1.73 m upon their entry into the cohort with more than 3 months of follow-up from January 2002 to August 2016. Cox regression models were used to estimate the association between LD and CKD development. Results Among the 5384 patients included, 1341 (24.9%) developed LD during the follow-up. The mean follow-up time was 72.3 months (SD ±48.4). In total, 252 patients (4.7%) reached the primary endpoint after a median time of 51.3 months (±SD 39.9 months) from inclusion. A diagnosis of LD significantly increased the risk of an eGFR on univariate analysis (hazard ratio [HR] = 2.72; 95% confidence interval [95% CI] = 2.07-3.58; < 0.001) and remained significantly higher after adjustment for known HIV and non-HIV risk factors for CKD (HR = 2.37; 95% CI = 1.67-3.36; < 0.001). The effect of LD on CKD was not mediated through the use of nephrotoxic antiretroviral drugs. Conclusion Lipodystrophy syndrome is independently associated with CKD after adjustment for previously reported risk factors.