Objective: Failure to dose adjust for renal insufficiency during hospitalization can be a common cause for medication errors and are an important function for clinicians. We examined the prevalence, mortality and length of stay (LOS) for cases that exhibited changes in renal function during hospitalization. Methods: We retrospectively analyzed 1,011,055 non-dialysis admissions who had at least two serum creatinine values during hospital stay across 74 hospitals that provided electronic laboratory results from 2003-2006. We used a modified Cockcroft-Gault (140-age)/SCr (x 0.85 for females) to determine baseline and changing creatinine clearance (eCrCl, ml/min). Cases were stratified based on eCrCl as normal (= 81 ml/min), mild (50-80 ml/min), moderate (16-49 ml/min), and advanced (= 15 ml/min). Worsening or improvement was defined as cases that moved one or more eCrCl strata to another during hospitalization. Unadjusted hospital mortality (95% CI) and median LOS were evaluated. Results: On admission 29.6% had normal, 34.4% had mild, 34.1% had moderate, and 1.9% had advanced eCrCl. Of these cases the eCrCl remained the same in 79.2%, worsened in 11.6% and improved in 9.2%. Mortality and median LOS was highest for worsening eCrCl (7.9 [CI:7.8-8.1] and 6 days) followed by those remaining the same (2.8 [CI:2.8-2.9] and 4 days) and those with improving eCrCl (1.8 [CI:1.7-1.9] and 4 days). Cases with = 2 strata worsening in eCrCl (0.5% of cases) had higher mortality and LOS (25.9 [CI:24.7-27.1] and 10 days) than those with moderate (5.0 [CI:4.9-5.1] and 5 days, 28.8% of cases) or advanced (13.3 [CI:12.7-13.8] and 5 days, 1.5% of cases) eCrCl that remained the same. Conclusion: Both improvement and worsening renal function necessitating potential dosage adjustment are common during hospitalization. Mortality and LOS is higher for cases that had worsening renal function. Comprehensive renal dosing programs have the potential of improving medication safety and related outcomes.