Liver transplantation (LT) provides optimal long-term disease-free survival for hepatocellular carcinoma (HCC). High pre-LT alpha-fetoprotein (AFP) has been associated with HCC recurrence, but it is unclear whether a drop in AFP or locoregional therapy impacts survival/recurrence after LT. LT-recipients transplanted for HCC in three centers (UNOS Region 6) were reviewed (2006–2009) for demographics, tumor characteristics, locoregional therapy, AFP, recurrence, and survival. Among 211 LT recipients (mean age 56.4 yr, 83% male, mean MELD 12.2), 94% met Milan criteria and 61% received locoregional therapy. Mean disease-free survival (DFS) was 1549.7 d, and 84% are currently alive. Factors affecting DFS included recurrence (RR, 0.074; 95% CI, 0.038–0.14), normal peak AFP (29.6, 95% CI, 2.96–296.3), peak AFP >400 (RR, 0.15; 95% CI, 0.03–0.73) and AFP at LT >400 (RR, 15.5; 95% CI, 2.4–100.5). Twenty-one patients had recurrence and were more likely beyond Milan criteria (5/23(21%) vs. 8/220 (4%), p = 0.0038), with peak AFP >400 and AFP at LT >400 (p = 0.001). Locoregional therapy did not affect mean DFS (1458.0 vs. 1603.8 d, p = 0.05) or recurrence (12.5% vs. 6%). Predictors of recurrence were similar to previous studies, including high AFP and tumor outside Milan criteria. While locoregional therapy itself did not affect DFS/recurrence, a decrease in AFP pre-transplant appears to positively influence outcomes in those who received locoregional therapy.