Context: Intermittent subglottic drainage (ISD) of secretions is recommended for prevention of ventilator-associated pneumonia (VAP) as it reduces microaspiration from the area around the cuff. Poor suction techniques can contribute to VAP, hence closed suction system (CSS) may have theoretical benefit in VAP prevention. Combination of these two techniques may provide added advantage. Aims: To study the influence of ISD with/without CSS on the incidence of VAP. Materials and Methods: Data from 311 patients requiring mechanical ventilation (MV) for more than 72 hours were collected retrospectively. They were divided into four groups as follows: group A, no intervention; group B, only CSS; group C, only ISD; and group D, ISD with CSS. These groups were compared with respect to incidence of VAP, duration of MV, length of ICU and hospital stay and ICU mortality. Results: Patients in the four groups were comparable with respect to age, sex ratio and admission Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Incidence of VAP per 1000 ventilator days in groups A, B, C, and D were 25, 23.9, 15.7 and 14.3, respectively (P=0.04). There was no significant difference in the duration of MV (P=0.33), length of ICU (P=0.55) and hospital stay (P=0.36) and ICU mortality (P=0.9) among the four groups. Conclusions: ISD of secretions reduces the incidence of VAP. CSS alone or in combination with ISD has no significant effect on VAP incidence. Hence, ISD may be recommended for VAP prevention, but indications other than VAP prevention should determine the type of the suction system.