In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.