PURPOSE To compare the demarcation line depth after contact lens-assisted corneal crosslinking (CXL) for progressive keratoconus using dextran-based and hydroxypropyl methylcellulose (HPMC)-based riboflavin solutions. SETTING Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India. DESIGN Retrospective case series. METHODS Patients with preoperative epithelium-on (epi-on) minimum corneal thickness between 350 μm and 450 μm having contact lens-assisted CXL for progressive keratoconus were crosslinked with isoosmolar 0.1% riboflavin in 20% dextran 500 or HPMC 1.1%. The primary outcome measure was the mean demarcation line depth measured 1 month postoperatively on anterior-segment optical coherence tomography. The secondary outcome measure was change in endothelial cell density (ECD) 6 months from baseline. RESULTS The study comprised 21 patients (21 eyes, 9 in the HPMC group and 12 in the dextran group). The mean demarcation line depth was deeper in the HPMC group (308.22 μm ± 84.19 [SD]) than in the dextran group (235.33 ± 64.87 μm) (P < .04). This difference remained significant (P = .02) even after controlling for the preoperative lesser epi-on minimum corneal thickness in the HPMC group (385.56 ±13.81 μm) versus the dextran group (413.08 ± 29.58 μm) (P < .02). The ECD 6 months after contact lens-assisted CXL was comparable to the baseline levels in both groups (P = .19 and P = .09, respectively). CONCLUSION During contact lens-assisted CXL, HPMC-based riboflavin seemed to be associated with a deeper demarcation line than dextran-based riboflavin, although both solutions were safe for the endothelium at 6 months.