OBJECTIVE: To explore the effect of proton pump inhibitors (PPI) and enteral nutrition (EN) on the incidence rate of hospital-acquired pneumonia (HAP) after stroke. METHODS: 329 stroke patients collected during Jul. 2013 to Jan. 2015 were divided into PPI group (160 cases), EN group (113 cases), combination group (56 cases). PPI group was given PPI orally, EN group given EN via nasogastric tube, and combination group given PPI and EN. The incidence of HAP, the effects of different medication course and timing on the incidence rate of HAP were observed in all groups, and the incidence of stress ulcer was recorded. RESULTS: HAP rate was 21.88% in PPI group, 30.09% in EN group, 57.14% in combination group, with statistical significance (P<0.05). In PPI group, the course of oral PPI was (16.21±6.84)d in HAP patients and (5.86±2.85)d in patients without HAP, with statistical significance (P<0.05). In EN group, the rate of early treatment was 35.29% in HAP patients and 67.09% in patients without HAP, with statistical significance (P<0.05). In combination group, the HAP rate of long-term PPI and non-early EN was 23.12%; that of long-term PPI and early EN was 14.29%; that of short-term PPI and non-early EN was 10.71%; that of short-term PPI and early EN was 3.56%, with statistical significance among groups (P<0.05). The incidence rate of stress ulcer was 1.88% in PPI group, 3.54% in EN group, 12.50% in combination group, with statistical significance among groups (P<0.05). CONCLUSIONS: The incidence rate of HAP can be reduce effectively by early EN and short-term use of PPI, and PPI combined with EN can not reduce the incidence of stress ulcer, but increase the rate of HAP.