OBJECTIVE: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC). DESIGN: Retrospective case-control study. SETTING: Kaiser Permanente Northern California (KPNC), a large population based-health maintenance organization. PATIENTS: Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer. MAIN EXPOSURE MEASURE: Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model). RESULTS: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk. CONCLUSION: Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk.