Traffic-generated air pollution and noise have both been linked to cardiovascular morbidity. Since traffic is a shared source, there is potential for correlated exposures that may lead to confounding in epidemiologic studies. As part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), 2-week NO and NO2 concentrations were measured at up to 105 locations, selected primarily to characterize gradients near major roads, in each of 9 US communities. We measured 5-min A-weighted equivalent continuous sound pressure levels (Leq) and ultrafine particle (UFP) counts at a subset of these NO/NO2 monitoring locations in Chicago, IL (N = 69 in December 2006; N = 36 in April 2007) and Riverside County, CA (N = 46 in April 2007). Leq and UFP were measured during non-“rush hour” periods (10:00–16:00) to maximize comparability between measurements. We evaluated roadway proximity exposure surrogates in relation to the measured levels, estimated noise–air pollution correlation coefficients, and evaluated the impact of regional-scale pollution gradients, wind direction, and roadway proximity on the correlations. Five-minute Leq measurements in December 2006 and April 2007 were highly correlated (r = 0.84), and measurements made at different times of day were similar (coefficients of variation: 0.5–13%), indicating that 5-min measurements are representative of long-term Leq. Binary and continuous roadway proximity metrics characterized Leq as well or better than NO or NO2. We found strong regional-scale gradients in NO and NO2, particularly in Chicago, but only weak regional-scale gradients in Leq and UFP. Leq was most consistently correlated with NO, but the correlations were moderate (0.20–0.60). After removing the influence of regional-scale gradients the correlations generally increased (Leq–NO: r = 0.49–0.62), and correlations downwind of major roads (Leq–NO: r = 0.53–0.74) were consistently higher than those upwind (0.35–0.65). There was not a consistent effect of roadway proximity on the correlations. In conclusion, roadway proximity variables are not unique exposure surrogates in studies of endpoints hypothesized to be related to both air pollution and noise. Moderate correlations between traffic-generated air pollution and noise suggest the possibility of confounding, which might be minimized by considering regional pollution gradients and/or prevailing wind direction(s) in epidemiologic studies.