Background The anterolateral thigh (ALT) flap is a workhorse flap in head and neck cancer reconstruction. The anteromedial thigh (AMT) flap was developed as a rescue or alternative flap whenever the ALT flap is not available; however, the harvest of AMT flap seems to be more challenging in the sense that perforators have multiple variations. This study was designed to compare the outcome of the AMT and ALT flaps in head and neck cancer reconstruction. Methods A total of 1,547 ALT and 57 AMT flaps were used for head and neck cancer reconstruction between March 1, 2008 and February 28, 2017. Differences in patient and operative characteristics were compared between the patients undergoing AMT and ALT flap reconstruction. The primary outcome of the free flap was its survival or failure, while the second outcome was the associated complications. Results Compared to those who had ALT flap reconstruction, the patients who underwent AMT flap reconstruction had a higher rate of conditions that required reconstruction after previous cancer ablation and recurrence but a lower rate of primary cancer and deeply located cancer. Analysis of the 40 well‐balanced pairs of propensity‐score‐matched patient cohorts revealed that the AMT flaps were associated with a significantly higher failure rate than the ALT flaps (15.0 vs. 0.0%, respectively; p = .026). Conclusion This study revealed that AMT flaps were associated with a significantly higher failure rate than ALT flaps in head and neck cancer reconstruction in the cohort of total patients and the propensity‐score‐matched cohorts.