To evaluate the effect of the topical instillation of hyaluronic acid eye drops with different viscosity on soft contact lens wettability and comfort. Methods: A randomized and participant-masked study was performed, involving 20 participants (25.462.6 years). One eye wore hydrogel (ocufilcon D) contact lenses, and another eye wore silicone-hydrogel (somofilcon A) contact lenses. The in vivo wettability tear film surface quality (TFSQ) index and comfort were measured before and after the instillation of different eye drops: saline solution (control) and 0.1%, 0.2%, and 0.3% hyaluronic acid. Results: Compared with saline solution, the instillation of 0.1%, 0.2%, and 0.3% hyaluronic acid improved the in vivo wettability of the hydrogel contact lenses by decreasing their TFSQ mean for 5, 10, and 30 min, respectively (P,0.05). During silicone-hydrogel contact lens wear, the hyaluronic acid did not affect wettability because there were no changes in TFSQ mean (P$0.05), but the 0.3% hyaluronic acid produced a decrease in comfort for the first 3 min (P,0.05). Conclusions: The instillation of hyaluronic acid eye drops increased the in vivo wettability of the hydrogel contact lens, and the duration of this effect was directly related to its concentration and viscosity.