<i>Background:</i> Mean diameter or longest diameter are the 2 most frequently used parameters for wheal response assessment after skin prick testing (SPT). We aimed to compare these 2 parameters taking as gold standard the surface of the wheal skin response. <i>Patients and Methods:</i> Patients suspected of having an allergic reaction against inhalant allergens have been skin prick tested using the Pan-European GA²LEN SPT panel. Fifteen minutes later, macroscopically evident wheal and flare reactions were marked with a pen and transferred to paper with a transparent scotch tape. Each paper-transferred wheal was scanned with an ordinary scanner, and its surface-corresponding maximum perpendicular diameters and longest diameters were measured using a computer software application for image recognition, developed for this purpose. Correlation coefficients (Spearman’s ρ) between surfaces and respective mean (ρ_mean) or longest (ρ_longest) diameters were calculated and subsequently compared. <i>Results:</i> 1,554 SPTs were performed in 74 patients. In 264, a macroscopically evident wheal and flare response was observed. Both mean and longest diameters correlated significantly with the wheal surfaces. However, ρ_longest was statistically significantly larger than ρ_mean when the surface of the wheal was >17 mm² (ρ_longest > 0.860 vs. ρ_mean < 0.660; p < 0.05).Such a surface corresponds to a maximum diameter of approximately 7 mm and a mean diameter of approximately 6 mm. Thus, the larger the surface of the wheal, the more appropriate the usage of the longest diameter. <i>Conclusions:</i> The longest wheal diameter alone seems to be a better surrogate marker of the wheal surface in comparison with the mean diameter. In addition, it is easier and faster to measure. Therefore, we propose this as the optimal methodology to evaluate SPTs.