Aim: The aim of this study was to identify predictors of worsening renal function (WRF) among hospitalized patients in the internal medicine department. Settings and Design: A one-year, hospital-based prospective study. Methods and Material: This study was carried out at the internal medicine department of Al-Watani governmental hospital, Palestine. Inclusion criteria were: hospitalization for at least 48 hours and availability of at least three serum creatinine (Scr) measurements. WRF was defined, per hospital stay, as an elevation in Scr of 0.5 mg/dL from baseline value if baseline Scr value was < 3mg/ dL and 1mg/dL if the baseline value was 3mg/dL. Baseline measurements were made at hospital admission. Statistical Analysis: Regression analysis (enter method) was carried out on two sets of variables: non-medication variables (Model I) and medication variables (Model II). Statistics was performed using SPSS version 15. Results: Three hundred and sixty one patients were included in this study. The prevalence of WRF among those who met the inclusion criteria was 40.2%. In the majority of cases, WRF started within the first 48 hrs of admission. Analysis of data indicated that eight variables were significantly associated with WRF: renal dysfunction (P < 0.0001), diabetes mellitus (P= 0.005), hypertension (HTN) (P < 0.0001), congestive heart failure (CHF) (P= 0.021), elderly (being > 65 years) (P= 0.003), number of diagnosis (P < 0.001), furosemide (P = 0.001) and calcium channel blockers (P= 0.01) administration at admission. Regression analysis indicated that HTN (P =0.033) and renal dysfunction (P= 0.007) were predictors of WRF in model I, while furosemide administration (P= 0.01) was the only predictor of WRF in model II. Conclusion: Hypertension, renal dysfunction and furosemide administration at hospital admission are predictors of WRF among hospitalized patients. Clinical characteristics available at hospital admission can be used to identify patients at increased risk for WRF. Patients receiving certain medications, especially loop diuretics, require close observation for potential development of WRF.