Spasticity from the upper motor neuron syndrome can result from a variety of conditions affecting the cortex or spinal cord. Some of the more common conditions associated with spasticity include spinal cord injury, cerebral palsy, and post-stroke syndrome. In this study we compared the efficacy and safety of baclofen vs tolperisone in spasticity. One hundred fifty patients with cerebral palsy or post stroke or spinal cord injury associated spasticity were enrolled in present study. Group I comprised of Seventy-five patients receiving baclofen and group II comprised of 75 patients receiving tolperisone. For efficacy measurement 4 evaluation methods were used, 1) Modified Ashworth Scale for muscle tone, 2) Medical research council scale for muscle strength and 3) Barthel Index for functional outcome 4) Coefficient of efficacy. In efficacy evaluation, both groups showed significant improvement in muscle tone, muscle strength and functional outcome at week 6 (Group I, 1.55±0.053, 2.79+0.032, 59.31±1.32; Group II, 1.57±0.053, 3.04±0.032, 73±1.32 respectively). In between the group analysis, there was no significant difference in muscle tone improvement in both the groups after 6 weeks (Group I, 1.055±0.053 vs Group II, 1.57±0.053, p>0.05). Group II showed non-significant but greater improvement in muscle strength (Week 6; Group I, 2.79±0.032 vs Group II, 3.04±0.032, p>0.07). Improvement in functional outcomes was greater in group II as compared to group I (Group I, 59.31±1.32 vs Group II, 73±1.32, p<0.05). Overall efficacy coefficient was greater for group II (3.6) as compared to group I (2.3). Baclofen showed more side effects compared to tolperisone in, asthenia being the most frequent. Tolperisone offers greater improvement in activities of daily living compared to baclofen. Tolperisone is more tolerable drug as compared to baclofen.