Introduction: Studies of EGFR mutation frequency in patients with non-small cell lung cancer (NSCLC) or lung adenocarcinoma were limited to clinical trials, convenient sample, retrospective studies of archived samples or studies involving advanced lung cancer only. Methods: A cross sectional, single center, prospective study of EGFR mutation status among patients with newly diagnosed lung adenocarcinoma attending University Malaya Medical Center over a 4-year-period. Results: Of 394 patients with adenocarcinoma, 166 (42.1%) were tested EGFR mutation-positive while the remaining 228 (57.9%) had EGFR wild-type tumour. Exon 19 deletion mutation was the most common EGFR mutation subtype (96 (24.4%)), followed by exon 21 L858R point mutation (64 (16.2%)). On univariate analysis, gender, smoking status and smoking pack-years (p< 0.001) were significantly associated with EGFR mutation status. Multivariate logistic regression analysis identified smoking status and smoking pack-year (p< 0.001) as independent predictive factors for EGFR mutation positivity. EGFR mutation frequency was significantly higher in never smokers (OR, 7.12; 95% CI, 3.79 – 13.38; p< 0.001) and previous smokers (OR, 2.45; 95% CI, 1.18 – 5.09; p=0.016). Compared to current or previous smokers of more than 50 pack-years, those who smoked less than 10 pack-years (OR, 7.70; 95% CI, 2.06 – 28.74; p=0.002) and 10-20 pack-years (OR, 3.42; 95% CI, 1.02 – 11.50; p=0.047) had significant higher frequency of EGFR mutation. Conclusion: EGFR mutation is common in Malaysian patients with lung adenocarcinoma. A never smoking status is a robust independent predictor of EGFR mutation positivity. EGFR mutation rate was inversely related to the amount of smoking, and is significantly lower in patients who smoked >20 pack-years.