Abstract: Objective To evaluate the safety and effectiveness of accelerated epi-off corneal collagen cross-linking(A-CXL)for progressive keratoconus. Methods This was a prospective,uncontrolled,interventional case series.Patients who received A-CXL in our center from September 2016 to September 2017 were recruited in this study.The visual acuity,diopter of spherical power(SD),diopter of cylindrical power(CD),endothelial cell count,corneal topography parameters,and corneal biomechanical parameters were examined preoperatively and at 1 week,1,3,6,12 months after surgery.All patients underwent anterior segment optical coherence tomography(AS-OCT)at 1 month after surgery.All the parameters were compared between different time points. Results This study involved 35 patients(48 eyes)who completed thorough reviews.Of the 35 cases,24 cases were male and 11 cases were female with average age of(22.83±3.87)years.The pre-operative and post-operative 1 week,1,3,6 and 12 months uncorrected visual acuities(LogMAR)were 0.70±0.20,0.73±0.20,0.64±0.19,0.63±0.21,0.57±0.20 and 0.56±0.20,respectively(P<0.01),and the best corrected visual acuities(LogMAR)were 0.38±0.23,0.34±0.20,0.31±0.18,0.23±0.14,0.21±0.14,and 0.16±0.09,respectively(P<0.01).Before surgery,and at 1 week,1 month,3 months,6 months and 12 months after surgery,the spherical power diopters(SD)were-5.00 D,-5.00 D,-5.00 D,-5.13 D,-5.00 D and-5.13 D,respectively;the SDs at 1 week,1 month and 3 months after surgery were smaller than that before operation,but the difference was not statistically significant(P>0.05).However,the SDs at post-operative 6 months and 12 months were significantly lower than that before surgery(P<0.01).The cylindrical power diopter(CD)before operation was-5.63 D,and it decreased to-5.00 D,-4.75 D,-5.00 D,-4.87 D and-4.50 D at 1 week,1 month,3 months,6 months and 12 months after operation,respectively(P<0.01).No considerably difference was observed in corneal endothelial cell counts(P>0.05).The central corneal thickness(TCT)before operation was 450.50 μm,which decreased to 444.50 μm at1 month,445.50μ m at 3 months and 447.00μm at 6 months after surgery(P<0.01).The maximum corneal curvature(K_max)was 56.70 D before operation,post-operative K_max values decreased to 55.70 D,54.95 D,54.70 D,54.65 D and 54.75 D at 1 week,1 month,3 months,6 months and 12 months,respectively(P<0.01).Comparative analysis showed a rise of corneal stiffness demonstrated by a significant increase of Stiffness Parameter A1(SP-A1)and significant decreases of both inverse concave radius(1/R)and deformation amplitude ratio(DA Ratio)(all P<0.05).Forty eyes(83.33%)showed transient irritation after surgery.Five eyes(10.42%)showed mild corneal haze.No serious perioperative complication was observed. Conclusion The A-CXL protocol can improve vision and biomechanical stability for progressive keratoconus effectively and safely.Further observation is needed for long term effectiveness assessment.