In Preble, NY 281 proceeds northeast at a fork that serves as the southern terminus of CR 108A (Steger Road). NY 281 and CR 108A parallel, with the route coming within a mile (1.6 km) of I-81. A short distance to the north, the route enters the hamlet of Preble, with NY 281 becoming a two-lane residential street. Intersecting CR 108B (Preble Road), NY 281 bends northeast at another fork, this time with CR 104 (Song Lake Road). On this northeastern stretch, the route enters a diamond interchange with I-81 (exit 13). After I-81, NY 281 continues northeast for a short distance through Preble, turning north on a parallel of the northbound lanes of I-81.