Nephrotoxic drugs prescriptions are often prescribed inappropriately by general practitioners (GPs), increasing the risk of chronic kidney disease (CKD). The aim of this study was to detect inappropriate prescriptions in patients with CKD and to identify their predictive factors. A retrospective study on patients with creatinine values recorded in the period 2014–2016 followed by 10 GPs was performed. The estimated glomerular filtration rate (eGFR) was used to identify CKD patients. The demographic and clinical characteristics and drugs prescriptions were collected. A descriptive analysis was conducted to compare the characteristics and logistic regression models to estimate the predictive factors of inappropriate prescriptions. Of 4098 patients with creatinine values recorded, 21.9% had an eGFR <60 mL/min/1.73 m2. Further, 56.8% received inappropriate prescriptions, with a significantly lower probability in subjects with at least a nephrologist visit (Adj OR 0.54 (95% CI 0.36–0.81)) and a greater probability in patients treated with more active substances (1.10 (1.08–1.12)), affected by more comorbidities (1.14 (1.06–1.230)), or with serious CKD (G4/G5 21.28 (7.36–61.57)). Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most used contraindicated drugs (48.5%), while acetylsalicylic acid was the most inappropriately prescribed (39.5%). Our results highlight the inappropriate prescriptions for CKD authorized by GPs and underline the need of strategies to improve prescribing patterns.