Vascular endothelial growth factor (VEGF) is involved in non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE), but little is known regarding the efficacy of bevacizumab (Bev) with carboplatin-paclitaxel (CP) for NSCLC with MPE. Chemotherapy-naive non-SQ NSCLC patients with MPE were eligible to participate. Pleurodesis before chemotherapy was not allowed. In the first cycle, the treated patients received only CP to prevent Bev-induced wound healing delayed after chest drainage. Subsequently, they received 2-6 cycles of CP with Bev. Patients who completed more than 4 cycles of CP and Bev without disease progression or severe toxicities continued to receive Bev alone as a maintenance therapy. The primary end point was overall response, although an increase in MPE was allowed in the first cycle. The VEGF levels in plasma and MPE were measured at baseline, and the VEGF levels in plasma were measured after 3 cycles of chemotherapy. Between September 2010 and June 2012, 23 patients were enrolled. The overall response rate was 60.8 %; the disease control rate was 87.0 %. Sixteen patients received maintenance therapy, following a median of 3 cycles. Median progression-free and overall survival times were 7.1 months (95 % confidence interval [CI], 5.6-9.4 months) and 11.7 months (95 % CI, 7.4-16.8 months), respectively. Most patients experienced severe hematological toxicities, including ≥grade 3 neutropenia; none experienced severe bleeding events. The MPE control rate improved on combining CP with Bev (CP, 78.3 %; CP with Bev, 91.3 %; P = 0.08). The median baseline VEGF level in MPE was 1798.6 (range 223.4-35,633.4) pg/mL. Plasma VEGF levels significantly decreased after 3 chemotherapy cycles (baseline, 513.6 ± 326.4 pg/mL, post-chemotherapy, 25.1 ± 14.1 pg/mL, P < 0.01). CP plus Bev was effective and tolerable in chemotherapy-naïve non-squamous NSCLC patients with MPE.