Background: In-hospital care of stroke patients can reduce the risk of death and disability. There is an emerging evidence for the routine use of care pathways (CPs) for acute stroke management. Our aim was to develop evidence-based CPs and test the hypothesis that acute stroke management by CPs is superior to that provided by conventional care. Materials and Methods: An acute stroke CP was designed in accordance with the recent American Stroke Association (ASA)/American Heart Association (AHA) stroke guidelines and the Indian Academy of Neurology (IAN) stroke management guidelines in India. A total of 162 acute stroke patients, who were managed within 72 hours of onset of their symptoms, were enrolled prospectively in two groups-the stroke care pathway (CP) arm (n = 77) and the conventional care (CC) arm (n = 85). The incidence of aspiration pneumonia, complications during the hospital stay, and death or dependency at discharge and at 90 days were among the main outcomes of our study. Results: The CP arm had a lower incidence of aspiration pneumonia (AP) in comparison with the CC arm (6.5% vs. 15.3%, risk ratio [RR] = 0.42, 95% confidence interval [CI] = 0.16-1.14, P = 0.062). The CP group had a decreased risk of requirement of mechanical ventilation (7.8% vs. 17.6%, odds ratio [OR] = 0.39, 95% CI = 0.14-1.07, P = 0.05). Barthel and modified Rankin Scale scores were similar in both the groups, but death at 90 days was significantly lesser in the CP arm (7.8% vs. 20%, P = 0.022). This benefit was most prominent in the Glasgow Coma Scale (GCS) subgroup scoring 9-15 (RR = 0.16, 95% CI = 0.03-0.71). There were no significant differences in the other outcome measures. Conclusion: Stroke CPs reduce the incidence of aspiration pneumonia, the need for mechanical ventilation, and the risk of death, when assessed at a follow-up of 90 days.