Objectives To compare the ablation margins and safety of microwave ablation (MWA) of perivascular versus non-perivascular liver metastases from colorectal cancer (CRC) and to determine the risk factors for local tumor progression (LTP) after perivascular MWA. Methods Between June 2017 and June 2019, 84 metastases were treated: 39 perivascular (<5 mm from a vessel >3 mm), and 46 non-perivascular. Perivascular metastases were treated with either conventional or optimized protocols (maximum power and/or several heating cycles after repositioning the needle regardless of the initial tumor dimensions). The mean diameter of metastases was 15.4 mm (SD: 7.56). Results Vascular proximity did not result in a significant difference in ablation margins. The technical success rate, primary efficacy, and secondary efficacy were 90%, 66%, and 83%, respectively. Perivascular location was not a risk factor for time to LTP (p = 0.49), RFS (p = 0.52), or OS (p = 0.54). LTP was statistically related to the presence of a colonic obstruction (p < 0.05), number of metastases at the time of diagnosis (p < 0.05), type of protocol (p < 0.05), ablation margins (p < 0.001) and LTP was proportional to the number of liver resections before MWA (p < 0.05). There was no LTP in tumors ablated with margins over 10 mm. Two grade 4 complications occurred. Conclusion MWA is an effective and safe treatment for perivascular liver metastases from CRC, provided that satisfactory margins are achieved. A maximalist attitude could be related to better local control.