Objectives This study aimed to identify the incidence of and factors associated with peripheral intravenous catheter/cannula (PIVC) first time insertion success (FTIS) in the emergency department (ED). Design Prospective cohort study. Setting Two tertiary EDs in Western Australia. Participants 879 ED patients. Primary outcome To identify factors affecting FTIS using univariate and multivariate logistic regression modelling. We created four models: patient factors only; clinician factors only; products and technology factors only and all factors model. We assessed each model's performance using area under the receiver operating characteristic curve. Results A total of 1201 PIVCs were inserted in 879 patients. The mean age was 60.3 (SD 22) years with slightly more females (52%). The FTIS rate was 73%, with 128 (15%) requiring a second attempt and 83 (9%) requiring three or more attempts. A small percentage (3%) had no recorded number of subsequent attempts. FTIS was related to the following patient factors: Age (for a 1-year increase in age: OR 0.99, 95% CI 0.983 to 0.998; p=0.0097); and target vein palpability: (always palpable vs never palpable: OR 3.53 95% CI 1.64 to 7.60; only palpable with tourniquet vs never palpable: OR 2.20, 95% CI 1.06 to 4.57; p=0.0014). Clinician factors related to FTIS include: clinicians with greater confidence (p<0.0001) and insertion experience (301-1000 vs <301: OR 1.54, 95% CI 1.02 to 2.34; >1000 vs <301: OR 2.07, 95% CI 1.41 to 3.04; p=0.0011). The final all factors model combining patient factors; clinician factors and product and technology factors has greater discriminative ability than specific factors models. It has a sensitivity of 74.26%, specificity of 57.69%, positive predictive value of 82.87% and negative predictive value of 44.85%. Conclusion A clinical decision, matching patients who have no palpable veins and are older, with clinicians with greater confidence and experience, will likely improve FTIS. Trialregistration number ANZCTRN12615000588594; Results.