Purpose: To evaluate the effects of mini-scleral lenses on visual acuity (VA) and visual functioning in patients with keratoconus. Methods: This prospective, interventional study examined the effects of mini-scleral lenses on VA and visual functioning in patients with keratoconus. Patients younger than 18 years or with a history of refractive surgery or corneal graft surgery were excluded. Patients were fitted with mini-Misa lenses, Senso mini-scleral lenses, or Zenlens mini-scleral lenses. Outcome measures were scleral lens-corrected VA and vision-related quality of life as assessed with the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-39). Results: Eighty-nine eyes of 50 keratoconus patients were included in the study. Median baseline logarithm of the minimal angle of resolution VA with habitual correction was 0.22 (range 0.02-1.04). Mini-scleral lens fitting resulted in a statistically significant visual improvement (median 0; P < 0.0001). At the 6-month follow-up, 11 patients (22%) had abandoned mini-scleral lens wear, primarily because of difficulties with lens handling (7 patients). Of the 39 patients with continued wear, 33 patients (84.6%) wore their lenses for a daily average of 12 hours. NEI-VFQ scoring in these patients showed significantly improved results for both visual functioning and socioemotional scales after scleral lens fitting (P < 0.0001). Conclusions: Mini-scleral lenses significantly improve VA and visual functioning on NEI-VFQ in patients with keratoconus. Difficulties with lens insertion and removal are the principal reason for lens dropout.