Purpose: Keratoconus affects patients' quality of life. No study has assessed the multivariate determinants of quality of life using the keratoconus end points assessment questionnaire (KEPAQ). Methods: This study included patients with keratoconus with no history of ocular surgery, who underwent clinical evaluation and tomographic imaging using a dual Scheimpflug/Placido device (Galilei G6). Emotional and functional quality of life was assessed using the KEPAQ. Multiple linear regression models were constructed for each KEPAQ subscale to adjust for confounding variables. Results: A total of 140 surgery-naïve patients with keratoconus were included, with a median age of 39 years and a male predominance (57.1%). For the KEPAQ-E subscale, the multivariate model was significant [F(84,10) = 2.79; adjusted R 2 = 0.160, P = 0.005], showing that female sex (β = −0.41) and worse corrected distance visual acuity in the better-seeing eye (β = −0.29) were associated with lower quality of life. Including the functional subscale score significantly enhanced the model's performance (adjusted R 2 = 0.464, β = 0.60). For the KEPAQ-F subscale, the model was also significant [F(84,10) = 2.37; adjusted R 2 = 0.127, P = 0.016], with corneal astigmatism in the better-seeing eye (β = −0.30) reducing quality of life. Adding the emotional subscale score improved the model (adjusted R 2 = 0.442, β = 0.62). Conclusions: Female sex, reduced vision, and corneal astigmatism negatively affect quality of life in patients with keratoconus. Nonetheless, patients' perceived impairment as measured in 1 subscale is a stronger predictor of overall quality of life than clinical and tomographic factors alone.