Background: To analyse the efficacy and patient satisfaction of fitting a mini-scleral lens (SL) after keratoplasty surgery in patients unsatisfied with their visual outcomes. Material and Methods: A retrospective chart review of 22 consecutive patients was performed between 2018 and 2019. Demographic data, indications for keratoplasty, ocular parameters, and visual results were evaluated. In addition, subjective visual quality (SVQ) and comfort, complications, daily wear time, and the reason for discontinuing SL wear during the 6-month follow-up were analysed. Results: Twenty-two eyes of 22 patients (6 females and 16 males; mean age 48.82 ± 17.19 years) were assessed. Keratoconus was the main indication for keratoplasty (9 eyes, 40.9%), followed by corneal opacities (5 eyes), and Fuchs endothelial dystrophy (4 eyes). High refractive anisometropia was found in 14 eyes (63.6%) and 6 eyes presented significant irregular astigmatism. LogMAR visual acuity improved significantly with SL when compared with the best spectacle-correction (mean, 0.12 ± 0.12 vs 0.52 ± 0.33, respectively; p < 0.01). Six patients discontinued SL wear (27.3%). Among the other 16 patients, the mean daily wear time was 11.47 ± 1.52 h; of these, 14 (87.5%) were successfully fitted and enjoyed favourable SVQ and comfort. No significant complications were found during the follow-up period. Conclusions: Mini-scleral lenses may be a safe and effective alternative for treating complicated eyes after keratoplasty; they may provide optimal visual rehabilitation and/or restore binocular vision with significant efficacy and patient satisfaction.