Introduction: Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established. Methods: WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS). Results: Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11–0.75], DRFS (HR 0.30, CI 0.08–0.99), DFS (HR 0.42, CI 0.21–0.86), and DSS (HR 0.16, CI 0.04–0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80–25.9), DFS (HR 2.98, CI 1.31–6.75), and DSS (HR 3.52, CI 1.14–10.9). Conclusion: Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation.