Purpose Gastroesophageal reflux disease (GERD) is common in patients with laryngeal cancer. However, the role of GERD in laryngeal cancer remains controversial because of poor matching and selection of inappropriate control groups in prior studies. We aimed to better understand this relationship by conducting a matched case-control study. Methods This study was based in a single tertiary care center over a 2-year period. Cases included all patients with a diagnosis of new laryngeal cancer presenting to the otolaryngology clinics. Two controls, derived from the internal medicine clinics, were matched to the cases on an individual basis for age (within 1 year), gender, ethnicity, and time of first visit to the institution (within 1 month). Data were extracted by chart review. Conditional logistic regression was used to assess the relationship between laryngeal cancer and GERD, tobacco, and alcohol consumption. Results A total of 96 cases were matched to 192 controls. On univariable analysis, the significant risk factors were current smoking, odds ratio (OR) 5.46 (95% confidence interval [CI], 2.59-11.50); alcohol, OR 1.97 (CI, 1.19-3.26); and GERD, OR 1.79 (CI, 1.03-3.11). On multivariable analysis, only smoking and GERD continued to be significantly associated with laryngeal cancer, OR 6.08 (CI, 2.82-13.10) and OR 2.11 (CI, 1.16-3.85), respectively. Conclusions Smoking and GERD are significant risk factors for laryngeal cancer and may have an independent incremental risk for laryngeal carcinogenesis.