INTRODUCTION: Pakistan has a high prevalence of oral cavity cancer (OCC) with a significant recurrence rate. This study aims to explore the factors associated with OCC recurrence in Karachi, Pakistan. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan, using data from the AKUH Cancer Registry. A total of 1692 biopsy-confirmed cases of OCC including cancers of mucosal lip, tongue, gum, oral cavity floor, palate and other subsites like retromolar area, diagnosed between May 2011 and December 2020, were included in our study. RESULTS: Of the 1692 patients, 611 (36.1%) experienced recurrence. Being male was associated with significantly increased odds of OCC recurrence compared to being female (Prevalence Odds Ratio (POR) = 1.70, 95% CI = 1.25-2.30). Moderately and poorly differentiated tumors had higher odds of recurrence (POR = 1.44, 95% CI = 1.02-2.02 and POR = 2.35, 95% CI = 1.49-3.71 respectively). Lymph node involvement was significantly associated with increased odds of recurrence. Patients with N1, N2 and N3 lymph node involvement had significantly higher odds of recurrence (POR = 1.45, 95% CI = 1.02-2.07 for N1, POR = 2.12, 95% CI = 1.57-2.87 for N2 and POR = 3.50, 95% CI = 1.72-7.11 for N3 respectively). Surgical treatment outside AKUH was associated with higher OCC recurrence (POR = 1.68, 95% CI = 1.12-2.50). Surgery alone (POR = 0.02, 95% CI = 0.00-0.16) and in combination with radiation (POR = 0.02, 95% CI = 0.00-0.16) or chemoradiation (POR = 0.04, 95% CI = 0.01-0.33) was protective against recurrence. CONCLUSION: This study's findings identified factors increasing oral cavity cancer recurrence, highlighting the importance of considering these factors in the management and follow up of patients with OCC. Understanding these factors will not only help enhance patient care, but also improve patient education about their disease prognosis. Further research is needed to explore the underlying mechanisms and develop targeted interventions to improve outcomes for patients with OCC.