Background: This study evaluated the association between baseline elevated CRP and lung cancer outcomes among adults with NSCLC who underwent surgery in the US. Methods: Optum Clinformatics Data Mart in the US (01/2007-09/2020) was used to identify adults with NSCLC who underwent lung cancer surgery and had at least 1 CRP measurement prior to or > 1 month following the index surgery. Baseline CRP levels were defined as the CRP closest to the index surgery in the pre-surgery cohort, and the CRP at least 1-month after in the post-surgery cohort. The association between elevated CRP (> 10 mg/L) and rate of NSCLC recurrence/risk of death was assessed separately for pre-surgery and post-surgery cohorts using multivariate regressions. The overall trend in CRP measurements over a 5-year period was examined using trend tests among those with persistently elevated CRP. Results: For adults in the pre-surgery cohort who had index lung cancer surgery between 2016-2020 (N = 104), after adjusting for age, sex, National Cancer Institute comorbidity, autoimmune disease, peripheral vascular disease, and smoking status, the adjusted-incidence rate ratio (IRR) for NSCLC recurrence was 2.17 (95% confidence interval [CI]: 1.03, 4.60; p < 0.05) among patients with elevated CRP compared with non-elevated CRP. A similar IRR (2.22 [95% CI: 1.05, 4.70]; p < 0.05) was observed among the 264 patients in the post-surgery cohort. Among the 234 patients in the pre-surgery cohort, there was a near two-fold increase in the risk of all-cause death associated with the elevated than the non-elevated CRP groups (odds ratio [OR]: 1.91 [95% CI: 1.06, 3.42]; p < 0.05), and there was a numerically increased risk associated with elevated baseline CRP for the post-surgery cohort (OR: 1.62 [95% CI: 0.88, 2.97]; p = 0.12). Among those with persistently elevated CRP prior to surgery, we observed a significant overall trend of increased CRP levels over the 5-year period. Conclusions: Using real world data in the US, results suggest that an elevated CRP at baseline is associated with a higher risk of NSCLC recurrence and mortality, for both pre- and post-surgery cohorts. An increasing trend of CRP level within 5 years prior to lung cancer surgery indicates the correlation of CRP (as a marker of inflammation) with tumor development. This study adds to a growing body of literature and may shed light into oncology treatments aimed at suppressing tumor-promoting inflammation.