Prior studies have shown that procedural learning is severely impaired in patients with diffuse cerebellar damage (cortical degeneration) as measured by the serial reaction time task (SRTT). We hypothesize that focal cerebellar lesions can also have lateralized effects on procedural learning. Our objective was to assess the effects of focal cerebellar lesions in procedural learning as measured by the SRTT. We studied 14 patients with single, unilateral vascular lesions in the territory of the posterior-inferior or superior cerebellar artery, who were compared with ten age- and sex-matched controls in a one-handed version of the SRTT. Patients with lesions at any other level of the brain or posterior fossa were excluded by cranial magnetic resonance imaging. Our results show that patients do not acquire procedural knowledge when performing the task with the hand ipsilateral to the lesion, but show normal learning with the contralateral hand. No correlation was found with the side, size, or vascular territory of the lesion. We conclude that procedural learning is impaired in hemispheric cerebellar lesions and involves only the hand ipsilateral to the lesion, which suggests a critical role for the cerebellum and/or crossed cerebellar-prefrontal connections in this type of learning.