Peperomia donnell-smithii is easily distinguished from P. urocarpa by the length/width ratio of the leaves. This ratio is 1.5–1.7 in P. donnell-smithii, whereas it is 1.0–1.2 in P. urocarpa, resulting in a significantly different leaf shape (figure). Furthermore, the leaf apex in P. donnell-smithii is long acuminate and the base is rounded. In P. urocarpa the apex is short acuminate and the base is cordate. In fresh specimens, the leaves of P. urocarpa exhibit a somewhat grey-blueish-green color, whereas they are vivid green in P. donnell-smithii. The leaves of P. donnell-smithii are minutely pilose on both sides whereas they are abaxially glabrous in P. urocarpa. P. donnell-smithii has axillary inflorescences whereas they are leaf-opposed in P. urocarpa. P. donnell-smithii is restricted to Costa Rica whereas P. urocarpa occurs in South America and the Caribbean islands.

Several publications list Peperomia donnell-smithii as a synonym of P. urocarpa. Most of of these works are floristic studies based on an inventory of (often misidentified) herbarium collections, rather than on thorough morphological comparison of the species in question. In July 2026, POWO listed 26 synonyms of P. urocarpa. This broad concept generally results in descriptions that mention a great variability in the characters, whereas P. urocarpa sensu strictu is a very homogeneous species [Guido Mathieu, pers. comm.]