We performed an extensive review of the literature to compare the efficacy of photodynamic therapy (PDT) to surgical resection, the current standard of care, in the treatment of adults with early-stage (T1-2N0M0) squamous cell carcinoma (SCC) of the oral cavity. Since patients who receive PDT are chosen with a high degree of selectivity, particular care was taken when extracting data for comparison. For outcomes measures, PDT was assessed in terms of a complete response to therapy, and surgery was evaluated in terms of locoregional control. Recurrences were also analyzed. We found 24 studies-12 for each treatment-to compare for this meta-analysis. In comparing a complete response to PDT and locoregional control with surgery, we found no statistically significant difference (mean difference [MD]: 1.166; 95% confidence interval [CI]: 0.479 to 2.839). With respect to recurrences, again no statistically significant difference was observed (MD: 0.552; 95% CI: 0.206 to 1.477). We conclude that PDT is as effective as primary surgical resection for the treatment of early-stage SCC of the oral cavity and that it is a valid function-preserving approach to treatment.