The presence of tumor-infiltrating lymphocytes has been shown to significantly improve clinical outcomes in many types of cancer. However, their effects on outcomes in patients with oropharyngeal cancer specifically have yet to be elucidated. We conducted a retrospective study in an effort to shed light on this issue. We reviewed the records of 48 consecutively presenting patients with oropharyngeal cancer, and we performed immunohistochemistry to analyze their archived paraffin-embedded tissue samples for the presence of CD3-positive tumor-infiltrating lymphocytes. We also used real-time polymerase chain reaction testing to look for human papillomavirus type 16 (HPV-16) in the tumors. We found that patients with large numbers of tumor-infiltrating lymphocytes (CD3high) had a significantly lower incidence of metastasis at presentation than did those with low numbers of tumor-infiltrating lymphocytes (CD3low) (40.0 vs. 88.5%; p = 0.001), regardless of HPV status. When HPV status was taken into account, the correlation between a high CD3 count and a lower rate of metastasis was maintained in the HPV-positive patients but not in the HPV-negative patients. We also found that the CD3high patients had higher rates of overall survival and disease-free survival at 3 and 5 years than did the CD3low patients; however, these differences only approached but did not reach statistical significance.