To investigate the potential improvement in visual acuity and subjective perception of image quality in patients with keratoconus using non-orthogonal correction (NOC) cylinder trial lenses where the steep and flat power meridians are set at angles less or greater than 90°. A set of NOC plano/cylindrical trial lenses, where the axes between the power meridians were set at a range of non-orthogonal angles, were used to refract 18 participants with keratoconus in whom 23 eyes were used for testing. Corneal elevation data were processed by bespoke MATLAB code from Pentacam Scheimpflug tomographer scans. Each participant first underwent subjective refraction using standard orthogonal cylinder trial lenses, and the monocular best-corrected visual acuity (BCVA, logMAR) was recorded for each eye. They then underwent a second subjective refraction using NOC cylinder trial lenses created for the study and completed a questionnaire to elicit their subjective appraisal of letter clarity and ghosting. Fourteen (61%) eyes demonstrated an increase in objective BCVA with the NOC versus the orthogonal correction; seven (30%) eyes showed no change and in two (9%) eyes, the BCVA was slightly worse. Further, 87% and 79% experienced an increase in letter clarity and a reduction in ghosting, respectively, independent of changes in BCVA. The majority of non-orthogonal angles were in the range of 80°-85°, and it was possible to refine the cylinder and axis of the NOC further compared with the orthogonal correction. All but one of the participants said they would be interested in trying non-orthogonal spectacles if the opportunity arose. Correcting irregular astigmatism in keratoconic individuals with non-orthogonal spectacle correction may provide benefit in terms of increased visual acuity, improvements in letter clarity and a reduction of ghosting effects. This type of correction has the potential to improve the overall quality of life for patients with keratoconus.