Although EGFRm NSCLC occurs mainly in non-smoking patients, most series report 20%-35% of cases in current or previous smokers. Broad molecular profiling of EGFRm NSCLC in smokers has not been reported. Surgically resected primary EGFR exon 19, 20 and 21 mutated NSCLC tumors from 106 patients were molecularly profiled by whole exome sequencing using the Illumina HiSeq2000 platform. Alignment and variant discovery analysis was performed according to GATK best practices workflow; 74 sequenced to a mean coverage of 65.1x. Demographics and outcomes were compared for smokers and non-smokers (non-S), and by mutation profile. Among 53 non-smokers and 21 smokers (5 current/recent within 10 years), 70% were female, 51% non-Asian, 40.5% >65 years of age and 58.1% had EGFR exon 19. Of the 74 patients, 51% were stage I, 19% stage II and 30% stage III+. Smoking was associated with male sex (p= 0.011) and non-Asian ethnicity (p=0.00002) but not age, stage or EGFR exon 19/20/21 subtype. Multiple “driver” mutations occurred in tumors of 23.8% smokers and 26.4% non-S. TP53/EGFR co-mutation occurred in 52.4% smokers and 47.2% non-S. There was no significant difference seen for TMB in smokers: median TMB in smokers 3(1.4-7.46) versus 2.7(0.96-3.95) in non-S (p=0.11). The strongest prognostic factor for OS and DFS was stage (I, II, III+) (p<0.0001 for each compared to stage I). Smoking history did not have a significant effect on survival: HR 1.61 (CI 0.78-3.32, p=0.2) or probability of relapse: HR 0.9 (CI 0.46-1.77, p=0.77). Smoking within 10 years of NSCLC diagnosis was not associated with shorter OS/DFS. Neither EGFRm subtype nor TP53/EGFR co-mutation was associated with probability of relapse or OS. High TMB was significantly associated with shorter survival: HR above vs below the median 2.37 (CI 1.12-5.01, p=0.024), but not probability of relapse: HR 1.67 (CI 0.88-3.19, p=0.12). A subset analysis found the effect of TMB on survival was significant in patients >65 years (p=0.004), but not in patients <65 years (p=0.95). Stage remains the strongest prognostic factor for survival and probability of relapse in completely resected EGFRm NSCLC. TMB appears to have an effect on survival outcomes, unlike smoking status, and this effect may be greater in patients older than 65 years.