Purpose To evaluate the variations in tear parameters and meibomian gland morphology after epithelial-on (epi-on) corneal collagen cross-linking (CXL) in keratoconus (KC) patients. Methods This prospective observational study included 38 KC eyes that underwent epithelium-on CXL. Thirty-three eyes of 33 stable KC patients with no prior CXL treatment formed the KC group and 35 eyes of 35 healthy volunteers were recruited as the control group. All participants were evaluated by Schirmer I test, first and average noninvasive tear break-up time (NITBUT), ocular surface disease index (OSDI) questionnaire, and meibography scores. The CXL patients were evaluated preoperatively and at the 1st, 3rd, and 6th months, and participants without any intervention (KC and control groups) were evaluated initially, at 1st, 3rd, and 6th months. Results The KC patients had significantly lower average NITBUT, higher OSDI scores, and impaired meibomian gland morphology than healthy individuals (NITBUT(seconds): KC, 12.8(2.4-17.6), healthy group (HG), 17.1(6.8-17.6); p = 0.012, OSDI: KC, 27.5(0.0-87.5), HG, 7.5(0.0-55.0); p < 0.001, p < 0.001, respectively). A significant difference was found in Schirmer values of the CXL group at 0-1st months, first NITBUT values at 1-6 months, and average NITBUT values at 1-3 and 1-6 months (p = 0.003, p = 0.001, p = 0.003, p = 0.001, respectively). All meibography parameters remained unchanged after CXL over a 6-month follow-up compared to initial measurements. Conclusions Even though the KC patients had lower NITBUT, higher OSDI scores, and increased meibomian gland disfunction, the CXL treatment did not significantly affect tear quantity, dry eye symptoms, and meibomian gland morphology.