It has been suggested that use of nonsteroidal anti-inflammatory drugs (NSAID) protects against Parkinson's disease, although the results are not consistent. We investigated the risk for Parkinson's disease in patients with osteoarthritis, who are typically intensive users of NSAID. By using the files of the National Danish Hospital Register for the period 1977-2006, we identified a cohort of 134,176 patients with osteoarthritis severe enough to have required subsequent hip or knee implant surgery. The number of first hospital contacts for Parkinson's disease among cohort members in 1986-2007 was compared with that expected from the age-, gender- and period-specific hospital contact rates of the general Danish population, and standardized incidence ratios (SIRs) and associated 95% confidence intervals (CIs) were derived. Cohort members were also linked to the Danish Cancer Register to estimate the SIRs for colorectal and lung cancer. We observed a slightly increased risk for Parkinson's disease among patients with osteoarthritis and subsequent implant surgery (SIR, 1.07; 95% CI, 0.99-1.16). Decreased SIRs were found for both colorectal cancer (0.92; 95% CI, 0.88-0.97), consistent with a high prevalence of NSAID use among cohort members, and lung cancer (0.77; 95% CI, 0.73-0.80), indicating a lower prevalence of smoking than usual. Our results do not support the hypothesis that patients with prolonged use of NSAID and other analgesics are at reduced risk for Parkinson's disease. A possible lower smoking prevalence among patients with osteoarthritis might explain the slightly increased risk for Parkinson's disease.