Background and Objectives: To compare ablation zone involution following microwave ablation (MWA) or irreversible electroporation (IRE) of liver tumors. Materials and Methods: MWA or IRE performed for colorectal cancer liver metastasis (CRLM) or hepatocellular carcinoma (HCC) during January 2011 to December 2015 were analyzed. Patients with a tumoral response on 1-year follow-up computed tomography (CT) were included. Generalized estimating equations were used to evaluate the differences between the two modalities on ablation zone involution observed on CT at 6 (M6) and 12 months (M12), and on laboratory values (total bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase, albumin, and platelets count). The likelihood ratio test was used to assess whether the association between ablation modalities and these outcomes differed over time. Results: Seventeen (17/44, 39%) women and 27 (27/44, 61%) men were included, with 25 HCC (25/44, 57%) and 19 CRLM (19/44, 43%) patients. IRE was used in 9 (9/19, 47%) CRLM and 5 (5/25, 20%) HCC patients, respectively. All other patients had MWA. Ablation zone size and involution between IRE and MWA differed significantly over time (interaction p < 0.01), with a mean of 241.04 vs. 771.08 mm2 (ratio 0.313; 95% CI, 0.165–0.592; p < 0.01) at M6 and 60.47 vs. 589.43 mm2 (ratio 0.103; 95% CI, 0.029–0.365; p < 0.01) at M12. Changes in liver enzymes did not differ significantly between IRE and MWA at both timepoints. Conclusions: Liver tumors treated with IRE underwent faster involution when compared to tumors treated with MWA, but liver enzymes levels were comparable.