Real‐world data on the first‐line treatment of patients with advanced non‐small cell lung cancer (NSCLC) are still limited. The NEPTUN study evaluated effectiveness and safety of first‐line nab‐paclitaxel (Abraxane) plus carboplatin (nab‐P/C) in patients with advanced NSCLC in routine clinical practice in Germany. Patients included in our study were aged ≥18 years, diagnosed with locally advanced or metastatic NSCLC and with decision for first‐line nab‐P/C in routine clinical practice. Primary objective was 6‐month progression‐free survival rate (PFS6), secondary objectives included overall survival (OS), overall response rate (ORR) and safety. From 2016 to 2019, 408 patients from 75 sites were enrolled. PFS6 was 39.5% (95% CI: 34.2‐44.8), median PFS was 5.1 months (95% CI: 4.6‐5.6), ORR was 42.9% (95% CI: 37.7‐48.2). Median OS was 10.5 months (95% CI: 9.2‐11.6). In subgroup analyses, median OS for squamous vs non‐squamous histology was 11.5 months (95% CI: 9.2‐13.8) vs 9.8 months (95% CI: 8.1‐11.3) and for patients aged ≥70 vs <70 years median OS was 12.4 months (95% CI: 9.8‐15.1) vs 9.6 months (95% CI: 7.7‐11.1). Adverse events (AEs) related to nab‐paclitaxel were reported in 247 (66.4%) patients, while carboplatin‐related AEs were documented in 224 (60.2%) patients. Most frequently related AEs were leukopenia (22.3%) for nab‐paclitaxel and anemia (20.2%) for carboplatin. Nab‐P/C‐related deaths were reported in 2 (0.5%) patients (sepsis and neutropenic sepsis). No new or unexpected safety signals emerged. These results support the effectiveness and safety of first‐line nab‐P/C in patients with advanced NSCLC reported in the pivotal trial and highlight the clinical value of this regimen in the real‐world setting. What's new? Non‐small cell lung cancer (NSCLC) patients often are diagnosed in advanced stages of disease, at which point, in cases without targetable mutations, first‐line therapy typically entails platinum‐based chemotherapy. A recommended therapy is albumin‐bound paclitaxel plus carboplatin combination (nab‐P/C). Here, the authors evaluated the use of first‐line nab‐P/C therapy in a real‐world setting in patients with locally advanced or metastatic NSCLC. Results show that survival was improved among nab‐P/C‐treated patients, with better outcomes observed particularly among patients age 70 and older and in those with mild to moderate renal impairment. Improvements in tumor response, independent of histological subtype, were also observed.