Reports evaluating simulation-based sigmoidoscopy training among nurses are scarce. The aim of this prospective nonrandomized study was to assess the performance of nurses in simulated sigmoidoscopy training and the potential impact on their performance of endoscopy unit experience, general professional experience, and skills in manual activities requiring coordinated maneuvers. Forty-four subjects were included: 12 nurses with (Group A) and 14 nurses without endoscopy unit experience (Group B) as well as 18 senior nursing students (Group C). All received simulator training in sigmoidoscopy. Participants were evaluated with respect to predetermined validated metrics. Skills in manual activities requiring coordinated maneuvers were analyzed to draw possible correlations with their performance. The total population required a median number of 5 attempts to achieve all predetermined goals. Groups A and C outperformed Group B regarding the number of attempts needed to achieve the predetermined percentage of visualized mucosa (p = .017, p = .027, respectively). Furthermore, Group A outperformed Group B regarding the predetermined duration of procedure (p = .046). A tendency was observed for fewer attempts needed to achieve the overall successful endoscopy in both Groups A and C compared with Group B. Increased score on playing stringed instruments was associated with decreased total time of procedure (rs = −.34, p = .03) and with decreased number of total attempts for successful endoscopy (rs = −.31, p = .046). This study suggests that training nurses and nursing students in simulated sigmoidoscopy is feasible by means of a proper training program. Experience in endoscopy unit and skills in manual activities have a positive impact on the training process.