The purpose of the study is to evaluate image quality and radiation exposure as a function of patient size for CT pulmonary angiography (CTPA) performed at reduced tube voltage and reduced intravenous (IV) contrast dose. We reviewed consecutive CTPAs performed between 9/1/2010 and 10/31/2010 on a 128-slice Siemens AS+ scanner using automated tube current modulation with quality reference mAs 200 and IV contrast concentration 370 mg I/ml followed by a saline flush: 99 scans at 120 kVp using 75 ml of contrast at 5 ml/s and 53 scans on patients lighter than 175 lbs at 100 kVp using 50 ml of contrast at 4 ml/s. We measured patient size (mean water-equivalent diameter) using a topogram analysis tool, signal (mean CT density) and noise (standard deviation) in the main pulmonary artery (MPA) on axial images, and calculated local CTDI(vol) from the kVp and mAs. Linear regression models were created for dependent variables ln(CTDI(vol)), signal, noise, and signal to noise ratio (SNR) as a function of independent variables size, age, gender, and kVp. After controlling for other variables, scanning at 100 kVp yielded CTDI(vol) reduction of 33 % (p < 0.0001), signal increase of 96 HU (p < 0.0001), and increased image noise (p < 0.0001), but without significant difference in SNR (p = 0.99). Relative to 120 kVp, 100-kVp CTPA allows simultaneous reduction of radiation exposure by 33 % and IV contrast dose by 33 % while maintaining image quality. Scanning at 100 kVp is recommended in all patients for whom the required mAs does not exceed maximum X-ray tube output.