Intrastromal corneal ring segments (ICRS) attain regularization of corneal surface in keratoconus (KC), while collagen cross-linking (CXL) halts or slows its progression. The long-arc 320° rings combined with CXL may have a dual-benefit synergistic effect of surface regularity and progression halt. This was a prospective case series study including eyes with progressive KC. Femto-assisted 320° ICRS implantation and epi-off CXL 8weeks later were carried out in all cases. Uncorrected (UCVA) and corrected distance visual acuity (CDVA) were assessed using Snellen's chart, while corneal tomography was evaluated using Scheimpflug imaging. Follow-up was carried out 3, 6, and 12months after the CXL. Thirty-two eyes of 32 patients with progressive KC were included, 18 males and 14 females, and the mean age was 23.1years. According to the Amsler-Krumeich classification, four eyes had stage 1 KC, 20 had stage 2 KC, and eight had stage 3 KC, and UCVA and CDVA improved from 0.1 ± 0.15 and 0.2 ± 0.19 to 0.4 ± 0.2 (P> 0.01) and 0.5 ± 0.2 (P> 0.01) respectively at 12months. Manifest refraction spherical equivalent was reduced from - 5.6 ± 2.3 to - 1.1 ± 1.3D at 12months after the procedure (P> 0.01). In addition, maximum keratometry was significantly reduced from 54.8 to 49.3 diopters (P> 0.01), while the asphericity index (Q value) has changed from - 1.4 to - 0.25 (P> 0.01) after 12months. No significant differences were detected between central (n = 12) and eccentric (n = 20) KC in all outcomes. The 320° ICRS-CXL protocol has improved the visual and the tomographic outcomes at 1year in our patients with progressive KC. No differences were detected between central and eccentric cases. Further larger studies could ensure the safety profile of the combined protocol.