· Purpose: We compared the tolerability and safety of a lyophilisate (Dry Drops) with conventional eye drops containing the same polymer and electrolytes. In Dry Drops the active ingredient is incorporated in a drop of hydrophilic polymer solution freeze-dried on the tip of a soft hydrophobic carrier strip. Upon contact with tear film and/or conjunctiva the lyophilisate immediately rehydrates and detaches from the carrier. · Methods: Dry Drops containing HPMC as active ingredient and a preservative-free tear film substitute were applied to 64 eyes of 32 healthy volunteers according to a 2² factorial design in an open-label, cross-over, randomised study. Tolerability and safety were quantified and qualified at 0.5, 2, 5 and 10 min after administration via slit-lamp biomicroscopy, questionnaire and visual analogue scales. · Results: The differences between Dry Drops and conventional eye drops were not statistically significant. The initial sensation of Dry Drops was slightly less uncomfortable than that of the conventional ophthalmic solution. None of the eyes showed any clinical findings with safety implications. · Conclusion: The safety and tolerability of a new application form were demonstrated in this phase I study. The improved chemical stability, exact dosing, reduced risk of lesions to the eye surface and good tolerability suggest that the new application device has promise for treatment in ophthalmology as well as in other medical subspecialties.