Rationale & Objective: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)—particularly those that incorporate multiple filtration markers. Study Design: Cross-sectional diagnostic test substudy of a randomized clinical trial. Setting & Participants: Adults ≥ 65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. Tests Compared: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, β-trace protein (BTP) and/or β₂-microglobulin (B2M). Outcome: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). Results: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9 mL/min/1.73 m²). Among the creatinine-based equations, the 2009 CKD-EPI_cr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPI_comb equation yielded the smallest relative bias (−3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPI_comb, the CKD-EPI_panel equation yielded a smaller RMSE (0.136) but larger relative bias (−4.0%) and inaccuracy (5.7%). Limitations: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. Conclusions: The 2009 CKD-EPI_cr, 2021 CKD-EPI_comb, and CKD-EPI_panel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. Funding: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). Trial Registration: Registered at ClinicalTrials.gov with registration number NCT03741283. Plain-Language Summary: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as β-trace protein and β₂-microglobulin did not further improve accuracy.