Cigarette smoking remains the leading cause of preventable death in the United States. Traditional in-clinic cessation interventions may fail to intervene and interrupt the rapid progression to relapse that typically occurs following a quit attempt. The ability to detect actual smoking behavior in real-time is a measurement challenge for health behavior research and intervention. The successful detection of real-time smoking through mobile health (mHealth) methodology has substantial implications for developing highly efficacious treatment interventions. The current study was aimed at further developing and testing the ability of inertial sensors to detect cigarette smoking arm movements among smokers. The current study involved four smokers who smoked six cigarettes each in a laboratory-based assessment. Participants were outfitted with four inertial body movement sensors on the arms, which were used to detect smoking events at two levels: the puff level and the cigarette level. Two different algorithms (Support Vector Machines (SVM) and Edge-Detection based learning) were trained to detect the features of arm movement sequences transmitted by the sensors that corresponded with each level. The results showed that performance of the SVM algorithm at the cigarette level exceeded detection at the individual puff level, with low rates of false positive puff detection. The current study is the second in a line of programmatic research demonstrating the proof-of-concept for sensor-based tracking of smoking, based on movements of the arm and wrist. This study demonstrates efficacy in a real-world clinical inpatient setting and is the first to provide a detection rate against direct observation, enabling calculation of true and false positive rates. The study results indicate that the approach performs very well with some participants, whereas some challenges remain with participants who generate more frequent non-smoking movements near the face. Future work may allow for tracking smoking in real-world environments, which would facilitate developing more effective, just-in-time smoking cessation interventions.