Pembrolizumab is currently the drug for the first-line treatment of stage-IV non-small cell lung cancer. The objective of this study is to measure the effectiveness of pembrolizumab as a first-line treatment and to analyze its safety in real clinical practice. This was a retrospective study that included patients with metastatic non-small cell lung cancer who had received pembrolizumab as a first-line treatment between 1 June 2018 and 31 January 2021. Variables related to the patients, treatment, and drug's efficacy and safety were collected. A total of 50 patients were analyzed. The median real-world progression-free survival and real-world overall survival of those who received pembrolizumab in monotherapy were 10.5 months (95% CI: 2.3-18.6) and 18.9 months (95% CI: 16.9-20.8), respectively. The median real-world progression-free survival and real-world overall survival of those who received the drug with chemotherapy was 7.9 months (95% CI: 4.1-11.7) and 13.3 months (95% CI: 0.0-27), respectively. Mostly digestive (48.3%) and endocrine (41.4%) immune-related adverse events were detected among the patients who received pembrolizumab in monotherapy, whereas mostly digestive immune-related adverse events (85.7%) and hematological toxicities (71.5%) were observed in those treated with pembrolizumab plus chemotherapy. Pembrolizumab has proven its effectiveness in terms of increasing real-world progression-free survival and real-world overall survival in real clinical practice. The main adverse events were digestive toxicities with pembrolizumab in monotherapy and with chemotherapy.