Background: We conducted a pilot study to assess the effect of 0.1% diclofenac sodium eyedrops on the initial comfort of rigid gas permeable (RGP) contact lenses. Methods: A double-masked, placebo-controlled, crossover trial was performed on 20 unadapted subjects. In Phase I, subjects used either 0.1% diclofenac or placebo eyedrops four times per day for 3 days before RGP lenses were dispensed. Contact lenses were inserted on Day 4 and worn for 8 continuous hours. Eyedrops were used twice during the 8-hour period. Ocular symptoms were graded on a visual analog scale at six points during the day. Visual acuity and slitlamp examinations were performed at the same six study points. After a 2-week wash-out period, subjects received the opposite treatment in Phase II, following the same protocol used in Phase I. Results: The treatment effect was tested using the Mainland-Gart chi-square test. There was no statistically significant treatment effect (chi-square = 0.20, p = 0.653) on patient symptoms. Biomicroscopy findings were analyzed and, like-wise, showed no significant treatment effect (chi-square = 2.10, p = 0.15). Conclusions: Data from this pilot study showed no statistically significant reduction in symptoms or signs with diclofenac eyedrops.