Introduction The development and publication of clinical practice guidelines for acute low-back pain has resulted in evidence-based recommendations that have the potential to improve the quality and safety of care for acute low-back pain. Development and dissemination of guidelines may not, however, be sufficient to produce improvements in clinical practice; further investment in active implementation of guideline recommendations may be required. Further research is required to quantify the trade-off between the additional upfront cost of active implementation of guideline recommendations for low-back pain and any resulting improvements in clinical practice. Methods Cost-effectiveness analysis alongside the IMPLEMENT trial from a health sector perspective to compare active implementation of guideline recommendations via the IMPLEMENT intervention (plus standard dissemination) against standard dissemination alone. Results The base-case analysis suggests that delivery of the IMPLEMENT intervention dominates standard dissemination (less costly and more effective), yielding savings of 135 per x-ray referral avoided (- 462.93/3.43). However, confidence intervals around point estimates for the primary outcome suggest that - irrespective of willingness to pay (WTP) - we cannot be at least 95 confident that the IMPLEMENT intervention differs in value from standard dissemination. Conclusions Our findings demonstrate that moving beyond development and dissemination to active implementation entails a significant additional upfront investment that may not be offset by health gains and/or reductions in health service utilization of sufficient magnitude to render active implementation cost-effective.