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Stress ulcer is one of acute stroke complications. Giving ranitidine or omeprazole may prevent stress ulcer, but may increase the occurrence of pneumonia, thus it will affect the outcome of acute stroke patients. This study aimed to determine the differences in the effectiveness of ranitidine and omeprazole in the prevention of stress ulcer and its influence on the occurrence of pneumonia and outcome of acute stroke patients. The method was experimental with randomized control-group pretest-posttest design. The subjects were divided into 2 groups, and each group consist of 16 patients. The first group was given ranitidine 300 mg and the second group was given omeprazole 20 mg.  Patients were observed if stress ulcer and/or pneumonia occurred during hospitalization. Outcome was measured by the national institutes of health stroke scale (NIHSS) and modified rankin scale (mRS). From 32 subjects obtained, stress ulcer was found only in 1 (3.1%) patient who received ranitidine, while pneumonia was found in 3 (3.1%) patients who received ranitidine and 2 (6.2%) patients who received omeprazole, but the differences were not significant between the two groups (p = 0.31 and p = 0.54). There was no significant effect and difference effect on the administration of both medications to the outcome based on the NIHSS and mRS at day 14. These results indicate that ranitidine and omeprazole have equal effectiveness in the prevention of stress ulcer and also have equal effect on the occurrence of pneumonia, and both have no effect on the outcome of acute stroke patients.