Background: Understanding the molecular basis of lung cancer has led to the development of targeted agents with a significant clinical benefit. This benefit is confined to patients with specific molecular tumor characteristics. However, chemotherapy represents the backbone of treatment in fit patients and is associated with a significant overall survival prolongation and quality of life improvement. Aim: To evaluate the effect of a continuation maintenance therapy with paclitaxel in advanced NSCLC patients with weekly paclitaxel. Patients and Methods: The current study included patients with advanced non-small-cell lung cancer (NSCLC) (stage IIIB or IV) with performance status ≤ 2 who experienced good initial good response, or stable disease after receiving 4 cycles of paclitaxel carboplatin. Patients were randomized into 2 arms, the first arm received weekly paclitaxel (70 mg/m²) as continuation maintenance therapy for 3 weeks of 4 weeks cycle. The treatment was continued until disease progression or unacceptable toxicity (maintenance arm). The second arm was kept under observation (observation arm). Results: There was a better lung cancer symptoms scale in the maintenance arm. Both times to progression and overall survival for the maintenance arm was higher (P value 0.16 and 0.047, respectively). Treatment-related toxicities were significantly higher in the maintenance arm as compared to the observation arm (P value <0.001). Conclusion: Maintenance with paclitaxel can be a reasonable option in patients with NSCLC who experienced a complete or partial response after initial paclitaxel carboplatin combination.